Статті в журналах з теми "Concomitant morphogenesis"
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1
Soffer, Arad, Adnan Mahly, Krishnanand Padmanabhan, Jonathan Cohen, Orit Adir, Eidan Loushi, Yaron Fuchs, Scott E. Williams, and Chen Luxenburg. "Apoptosis and tissue thinning contribute to symmetric cell division in the developing mouse epidermis in a nonautonomous way." PLOS Biology 20, no. 8 (August 15, 2022): e3001756. http://dx.doi.org/10.1371/journal.pbio.3001756.
Анотація:
Mitotic spindle orientation (SO) is a conserved mechanism that governs cell fate and tissue morphogenesis. In the developing epidermis, a balance between self-renewing symmetric divisions and differentiative asymmetric divisions is necessary for normal development. While the cellular machinery that executes SO is well characterized, the extrinsic cues that guide it are poorly understood. Here, we identified the basal cell adhesion molecule (BCAM), a β1 integrin coreceptor, as a novel regulator of epidermal morphogenesis. In utero RNAi-mediated depletion of Bcam in the mouse embryo did not hinder β1 integrin distribution or cell adhesion and polarity. However, Bcam depletion promoted apoptosis, thinning of the epidermis, and symmetric cell division, and the defects were reversed by concomitant overexpression of the apoptosis inhibitor Xiap. Moreover, in mosaic epidermis, depletion of Bcam or Xiap induced symmetric divisions in neighboring wild-type cells. These results identify apoptosis and epidermal architecture as extrinsic cues that guide SO in the developing epidermis.
2
Wu, Wei, Shinji Kitamura, David M. Truong, Timo Rieg, Volker Vallon, Hiroyuki Sakurai, Kevin T. Bush, David R. Vera, Robert S. Ross та Sanjay K. Nigam. "β1-Integrin is required for kidney collecting duct morphogenesis and maintenance of renal function". American Journal of Physiology-Renal Physiology 297, № 1 (липень 2009): F210—F217. http://dx.doi.org/10.1152/ajprenal.90260.2008.
Анотація:
Deletion of integrin-β1 ( Itgb1) in the kidney collecting system led to progressive renal dysfunction and polyuria. The defect in the concentrating ability of the kidney was concomitant with decreased medullary collecting duct expression of aquaporin-2 and arginine vasopressin receptor 2, while histological examination revealed hypoplastic renal medullary collecting ducts characterized by increased apoptosis, ectasia and cyst formation. In addition, a range of defects from small kidneys with cysts and dilated tubules to bilateral renal agenesis was observed. This was likely due to altered growth and branching morphogenesis of the ureteric bud (the progenitor tissue of the renal collecting system), despite the apparent ability of the ureteric bud-derived cells to induce differentiation of the metanephric mesenchyme. These data not only support a role for Itgb1 in the development of the renal collecting system but also raise the possibility that Itgb1 links morphogenesis to terminal differentiation and ultimately collecting duct function and/or maintenance.
3
Corellou, Florence, Colin Brownlee, Bernard Kloareg, and François-Yves Bouget. "Cell cycle-dependent control of polarised development by a cyclin-dependent kinase-like protein in theFucuszygote." Development 128, no. 21 (November 1, 2001): 4383–92. http://dx.doi.org/10.1242/dev.128.21.4383.
Анотація:
Although iterative development can be uncoupled from morphogenesis in plant organs, the relationship between the cell cycle and developmental events is not well established in embryos. Zygotes of fucoid algae, including Fucus and Pelvetia are particularly well suited for studying the interaction(s) between cell cycle progression and the early morphogenetic events, as the establishment of polarity and its morphogenetic expression, i.e. germination, and the first cell cycle are concomitant. We have previously demonstrated that, in Fucus zygotes, various aspects of cell cycle progression are tightly controlled by cyclin-dependent kinase (CDK)-like proteins, including two PSTAIRE CDK-like proteins, p34 and p32, which are synthesised after fertilisation. We show that specific inhibition of CDK-like proteins, either with purine derivatives such as olomoucine and amino-purvalanol or by microinjection of the CDK inhibitor p21cip1, prevents germination and cell division. Whereas direct inhibition of DNA replication by aphidicolin did not affect polarised development, olomoucine, which has previously been shown to prevent entry in S phase, and other purine derivatives also inhibited photopolarisation. Early microinjection of a monoclonal anti-PSTAIRE antibody also prevented germination and cell division. Only p34 had affinity for amino-purvalanol, suggesting that among PSTAIRE CDKs, this protein is the main target of purine derivatives. Models to account for the simultaneous control of early cell cycle progression and polarisation are proposed.
4
Hsu, Tzu-Han, Rey-Huei Chen, Yun-Hsin Cheng, and Chao-Wen Wang. "Lipid droplets are central organelles for meiosis II progression during yeast sporulation." Molecular Biology of the Cell 28, no. 3 (February 2017): 440–51. http://dx.doi.org/10.1091/mbc.e16-06-0375.
Анотація:
Neutral lipids, predominantly triacylglycerol (TAG) and sterol ester, are stored within the cellular organelles termed lipid droplets (LDs). Although it is believed that the major function of LDs is to supply the cell with energy and membranes, little is known about the cellular events directly involving LDs and their contents. In this study, we provide cytological evidence that LDs form direct contacts with the prospore membrane (PSM) that is synthesized de novo during meiosis II to sequester the dividing nuclei in sporulating yeast. Lipidomic analyses indicate that TAG lipolysis releases free fatty acids at a time that correlates well with meiosis II progression, concomitant with phospholipid remodeling. Mutants lacking TAG or impaired of TAG hydrolysis show spore wall assembly defects, supporting a role for TAG and/or its metabolites in spore wall morphogenesis. Not only does LD integrity influence spore wall assembly, LDs are also essential for other aspects of spore development. Yeast cells lacking LDs are severely defective in PSM growth and organization and display disrupted spindles, producing dead spores or even failing to form spores. Together these results link LD physiology directly to a unique membrane morphogenesis process critical for development.
5
Gambley, RL, and W. Dodd. "Effect of Hypocotyl Length on Morphogenesis of Explants of Cucumber (Cucumis sativus L.) in vitro." Functional Plant Biology 19, no. 2 (1992): 165. http://dx.doi.org/10.1071/pp9920165.
Анотація:
Explants of cucumber seedlings having different lengths of hypocotyl attached were grown axenically on Murashige and Skoog medium supplemented with kinetin (2 mg L-1). Multiple shoots developed from the apical regions of all explants. In this tissue shoots may also develop at the base of the hypocotyl, but this response is strongly dependent upon the length of the hypocotyl. As the length of the hypocotyl increased beyond 5 mm, there was a rapid reduction in basal shoot numbers and a concomitant increase in root production. We suggest that these responses are related not to the ratio or concentration of endogenous growth regulators but to different regions of sensitivity to growth regulators along the hypocotyl.
6
Panteris, Emmanuel, and Ioannis-Dimosthenis S. Adamakis. "Double Puzzle: Morphogenesis of the Bi-Layered Leaf Adaxial Epidermis of Magnolia grandiflora." Plants 11, no. 24 (December 9, 2022): 3437. http://dx.doi.org/10.3390/plants11243437.
Анотація:
Anticlinal ordinary epidermal cell wall waviness is a widespread feature found in the leaves of a variety of land plant species. However, it has not yet been encountered in leaves with multiple epidermides. Surprisingly, in Magnolia grandiflora leaves, ordinary epidermal cells in both layers of the bi-layered adaxial epidermis exhibit wavy anticlinal contour. During the development of the above cells, cortical microtubules are organized in anticlinally oriented bundles under the anticlinal walls, and radial arrays extending from the bundles at the edges of anticlinal and external periclinal walls, under the external periclinal walls. This microtubule pattern is followed by cell wall reinforcement with local thickenings, the cellulose microfibrils of which are parallel to the underlying microtubules. This specialized microtubule organization and concomitant cell wall reinforcement is initiated in the external epidermal layer, while hypodermis follows. The waviness pattern of each epidermal layer is unrelated to that of the other. The above findings are discussed in terms of morphogenetic mechanism induction and any implications in the functional significance of ordinary epidermal cell waviness.
7
Kim, J. Y., Y. G. Cha, S. W. Cho, E. J. Kim, M. J. Lee, J. M. Lee, J. Cai, H. Ohshima, and H. S. Jung. "Inhibition of Apoptosis in Early Tooth Development Alters Tooth Shape and Size." Journal of Dental Research 85, no. 6 (June 2006): 530–35. http://dx.doi.org/10.1177/154405910608500610.
Анотація:
Apoptosis plays important roles in various stages of organogenesis. In this study, we hypothesized that apoptosis would play an important role in tooth morphogenesis. We examined the role of apoptosis in early tooth development by using a caspase inhibitor, z-VAD-fmk, concomitant with in vitro organ culture and tooth germ transplantation into the kidney capsule. Inhibition of apoptosis at the early cap stage did not disrupt the cell proliferation level when compared with controls. However, the macroscopic morphology of mice molar teeth exhibited dramatic alterations after the inhibition of apoptosis. Crown height was reduced, and mesiodistal diameter was increased in a concentration-dependent manner with z-VAD-fmk treatment. Overall, apoptosis in the enamel knot would be necessary for the proper formation of molar teeth, including appropriate shape and size.
8
Ulanova, V. I., V. I. Mazurov, and V. A. Zinzerling. "Clinical and morphological characteristics of infective endocarditis." Clinical Medicine (Russian Journal) 98, no. 2 (July 15, 2020): 115–21. http://dx.doi.org/10.30629/0023-2149-2020-98-2-115-121.
Анотація:
The aim of the study was to identify the features of the clinical course and morphogenesis of infective endocarditis (IE) in HIVinfected injecting drug users with concomitant hepatitis C virus infection in comparison with the clinical and morphological picture of endocarditis in persons without drug dependence. It was found that the causative agent of IE in HIV-infected patients was staphylococcus aureus (71.8%), and in persons without drug dependence in the etiology of the disease the conditionally pathogenic flora prevailed. In HIV-infected drug-dependent patients, the tricuspid valve was affected (82.7%), and in persons without drug dependence — isolated aortic valve damage (40%) and combined mitral and aorticvalve lesions (36.4%). Purulent sepsis complications in drug-dependent patients with IE are less common than in patients without drug dependence due to immunosuppression, which is present in HIV-infected persons.
9
Proksch, S., T. Steinberg, S. Schulz, S. Sauerbier, E. Hellwig, and P. Tomakidi. "Environmental Biomechanics Substantiated by Defined Pillar Micropatterns Govern Behavior of Human Mesenchymal Stem Cells." Cell Transplantation 21, no. 11 (November 2012): 2455–69. http://dx.doi.org/10.3727/096368912x637037.
Анотація:
While evidence on the impact of the biomechanical environment elasticity on human mesenchymal stem cell (hMSC) behavior is growing, the aspect of micropatterning is still poorly understood. Thus, the present study aimed at investigating the influence of defined environmental micropatterning on hMSC behavior. Following characterization, hMSCs were grown on defined pillar micropatterns of 5, 7, 9, and 11 μm. With respect to cell behavior, primary hMSC adhesion was detected by indirect immunofluorescence (iIF) for paxillin, vinculin, integrin αV, and actin, while proliferation was visualized by histone H3. Morphogenesis was monitored by scanning electron microscopy and the expression of stem cell-specific biomarkers by real-time PCR. Favoritism of primary adhesion of hMSCs on pillar tops occurred at smaller pillar micropatterns, concomitant with cell flattening. While vinculin, integrin αV, and paxillin appeared initially more cytoplasmic, high pillar micropatterns favored a progressive redistribution with polarization to cell tension sites and at cell borders. Accomplishment of morphogenesis at day 3 revealed establishment of fully rotund cell somata at 5 μm, while hMSCs appeared progressively elongated at rising micropatterns. The hMSC proliferation capacity was influenced by pillar micropatterns and gene expression analysis of stem cell- and differentiation-associated biomarkers disclosed clear modulation by distinct pillar micropatterns. In response to environmental biomechanics, our results show that hMSC behavior is governed by pillar micropatterning. In turn, these findings may form the basis to prospectively direct lineage specificity of hMSCs in a customized fashion.
10
Chen, Yen-Ju, Kuan-Yi Wu, Shu-Fan Lin, Sung-Hsi Huang, Heng-Cheng Hsu, and Hong-Ming Hsu. "PIP2 regulating calcium signal modulates actin cytoskeleton-dependent cytoadherence and cytolytic capacity in the protozoan parasite Trichomonas vaginalis." PLOS Pathogens 19, no. 12 (December 18, 2023): e1011891. http://dx.doi.org/10.1371/journal.ppat.1011891.
Анотація:
Trichomonas vaginalis is a prevalent causative agent that causes trichomoniasis leading to uropathogenic inflammation in the host. The crucial role of the actin cytoskeleton in T. vaginalis cytoadherence has been established but the associated signaling has not been fully elucidated. The present study revealed that the T. vaginalis second messenger PIP2 is located in the recurrent flagellum of the less adherent isolate and is more abundant around the cell membrane of the adherent isolates. The T. vaginalis phosphatidylinositol-4-phosphate 5-kinase (TvPI4P5K) with conserved activity phosphorylating PI(4)P to PI(4, 5)P2 was highly expressed in the adherent isolate and partially colocalized with PIP2 on the plasma membrane but with discrete punctate signals in the cytoplasm. Plasma membrane PIP2 degradation by phospholipase C (PLC)-dependent pathway concomitant with increasing intracellular calcium during flagellate-amoeboid morphogenesis. This could be inhibited by Edelfosine or BAPTA simultaneously repressing parasite actin assembly, morphogenesis, and cytoadherence with inhibitory effects similar to the iron-depleted parasite, supporting the significance of PIP2 and iron in T. vaginalis colonization. Intriguingly, iron is required for the optimal expression and cell membrane trafficking of TvPI4P5K for in situ PIP2 production, which was diminished in the iron-depleted parasites. TvPI4P5K-mediated PIP2 signaling may coordinate with iron to modulate T. vaginalis contact-dependent cytolysis to influence host cell viability. These observations provide novel insights into T. vaginalis cytopathogenesis during the host-parasite interaction.
11
Hathaway, H. J., and B. D. Shur. "Mammary gland morphogenesis is inhibited in transgenic mice that overexpress cell surface beta1,4-galactosyltransferase." Development 122, no. 9 (September 1, 1996): 2859–72. http://dx.doi.org/10.1242/dev.122.9.2859.
Анотація:
Mammary gland morphogenesis is facilitated by a precise sequence of cell-cell and cell-matrix interactions, which are mediated in part through a variety of cell surface receptors and their ligands (Boudreau, N., Myers, C. and Bissell, M. J. (1995). Trends in Cell Biology 5, 1–4). Cell surface beta1,4-galactosyltransferase (GalTase) is one receptor that participates in a variety of cell-cell and cell-matrix interactions during fertilization and development, including mammary epithelial cell-matrix interactions (Barcellos-Hoff, M. H. (1992). Exp. Cell Res. 201, 225–234). To analyze GalTase function during mammary gland morphogenesis in vivo, we created transgenic animals that overexpress the long isoform of GalTase under the control of a heterologous promoter. As expected, mammary epithelial cells from transgenic animals had 2.3 times more GalTase activity on their cell surface than did wild-type cells. Homozygous transgenic females from multiple independent lines failed to lactate, whereas transgenic mice overexpressing the Golgi-localized short isoform of GalTase lactated normally. Glands from transgenic females overexpressing surface GalTase were characterized by abnormal and reduced ductal development with a concomitant reduction in alveolar expansion during pregnancy. The phenotype was not due to a defect in proliferation, since the mitotic index for transgenic and wild-type glands was similar. Morphological changes were accompanied by a dramatic reduction in the expression of milk-specific proteins. Immunohistochemical markers for epithelia and myoepithelia demonstrated that both cell types were present. To better understand how overexpression of surface GalTase impairs ductal morphogenesis, primary mammary epithelial cultures were established on basement membranes. Cultures derived from transgenic mammary glands were unable to form anastomosing networks of epithelial cells and failed to express milk-specific proteins, unlike wild-type mammary cultures that formed epithelial tubules and expressed milk proteins. Our results suggest that cell surface GalTase is an important mediator of mammary cell interaction with the extracellular matrix. Furthermore, perturbing surface GalTase levels inhibits the expression of mammary-specific gene products, implicating GalTase as a component of a receptor-mediated signal transduction pathway required for normal mammary gland differentiation.
12
Segal, Marisa, Kerry Bloom, and Steven I. Reed. "Bud6 Directs Sequential Microtubule Interactions with the Bud Tip and Bud Neck during Spindle Morphogenesis inSaccharomyces cerevisiae." Molecular Biology of the Cell 11, no. 11 (November 2000): 3689–702. http://dx.doi.org/10.1091/mbc.11.11.3689.
Анотація:
In budding yeast, spindle polarity relies on a precise temporal program of cytoplasmic microtubule–cortex interactions throughout spindle assembly. Loss of Clb5-dependent kinase activity under conditions of attenuated Cdc28 function disrupts this program, resulting in diploid-specific lethality. Here we show that polarity loss is tolerated by haploids due to a more prominent contribution of microtubule–neck interactions to spindle orientation inherent to haploids. These differences are mediated by the relative partition of Bud6 between the bud tip and bud neck, distinguishing haploids from diploids. Bud6 localizes initially to the bud tip and accumulates at the neck concomitant with spindle assembly. bud6Δmutant phenotypes are consistent with Bud6's role as a cortical cue for cytoplasmic microtubule capture. Moreover, mutations that affect Bud6 localization and partitioning disrupt the sequential program of microtubule–cortex interactions accordingly. These data support a model whereby Bud6 sequentially cues microtubule capture events at the bud tip followed by capture events at the bud neck, necessary for correct spindle morphogenesis and polarity.
13
Crepaldi, Tiziana, Alexis Gautreau, Paolo M. Comoglio, Daniel Louvard, and Monique Arpin. "Ezrin Is an Effector of Hepatocyte Growth Factor–mediated Migration and Morphogenesis in Epithelial Cells." Journal of Cell Biology 138, no. 2 (July 28, 1997): 423–34. http://dx.doi.org/10.1083/jcb.138.2.423.
Анотація:
The dissociation, migration, and remodeling of epithelial monolayers induced by hepatocyte growth factor (HGF) entail modifications in cell adhesion and in the actin cytoskeleton through unknown mechanisms. Here we report that ezrin, a membrane–cytoskeleton linker, is crucial to HGF-mediated morphogenesis in a polarized kidney-derived epithelial cell line, LLC-PK1. Ezrin is a substrate for the tyrosine kinase HGF receptor both in vitro and in vivo. HGF stimulation causes enrichment of ezrin recovered in the detergent-insoluble cytoskeleton fraction. Overproduction of wild-type ezrin, by stable transfection in LLC-PK1 cells, enhances cell migration and tubulogenesis induced by HGF stimulation. Overproduction of a truncated variant of ezrin causes mislocalization of endogenous ezrin from microvilli into lateral surfaces. This is concomitant with altered cell shape, characterized by loss of microvilli and cell flattening. Moreover, the truncated variant of ezrin impairs the morphogenic and motogenic response to HGF, thus suggesting a dominant-negative mechanism of action. Site-directed mutagenesis of ezrin codons Y145 and Y353 to phenylalanine does not affect the localization of ezrin at microvilli, but perturbs the motogenic and morphogenic responses to HGF. These results provide evidence that ezrin displays activities that can control cell shape and signaling.
14
Gallant, Claude V., Maja Sedic, Erin A. Chicoine, Teresa Ruiz, and Keith P. Mintz. "Membrane Morphology and Leukotoxin Secretion Are Associated with a Novel Membrane Protein of Aggregatibacter actinomycetemcomitans." Journal of Bacteriology 190, no. 17 (July 11, 2008): 5972–80. http://dx.doi.org/10.1128/jb.00548-08.
Анотація:
ABSTRACT Gram-negative bacteria display either a flat or an irregular outer membrane. The periodontal pathogen Aggregatibacter (Actinobacillus) actinomycetemcomitans has an irregular outer membrane. We have identified a gene that is associated with the biogenesis of this morphology. The gene is part of a three-gene operon and codes for a 141-kDa protein designated morphogenesis protein C (MorC), which is conserved in several gram-negative bacteria including Haemophilus influenzae and Pasteurella multocida. Insertional inactivation of this gene resulted in the conversion of an irregularly shaped membrane to a flat membrane. Associated with this morphological change were the autoaggregation of the bacteria during planktonic growth and a concomitant increase in the surface hydrophobicity of the bacterium. The absence of MorC also resulted in the loss of the secretion of leukotoxin but not the ltxA transcription. Our findings suggest that MorC is critical for membrane morphology and leukotoxin secretion in A. actinomycetemcomitans.
15
Chuang, Jen-Zen, Szu-Yi Chou, and Ching-Hwa Sung. "Chloride Intracellular Channel 4 Is Critical for the Epithelial Morphogenesis of RPE Cells and Retinal Attachment." Molecular Biology of the Cell 21, no. 17 (September 2010): 3017–28. http://dx.doi.org/10.1091/mbc.e09-10-0907.
Анотація:
Retinal detachment is a sight-threatening condition. The molecular mechanism underlying the adhesion between the RPE and photoreceptors is poorly understood because the intimate interactions between these two cell types are impossible to model and study in vitro. In this article, we show that chloride intracellular channel 4 (CLIC4) is enriched at apical RPE microvilli, which are interdigitated with the photoreceptor outer segment. We used a novel plasmid-based transfection method to cell-autonomously suppress CLIC4 in RPE in situ. CLIC4 silenced RPE cells exhibited a significant loss of apical microvilli and basal infoldings, reduced retinal adhesion, and epithelial-mesenchymal transition. Ectopically expressing ezrin failed to rescue the morphological changes exerted by CLIC4 silencing. Neural retinas adjacent to the CLIC4-suppressed RPE cells display severe dysplasia. Finally, a high level of aquaporin 1 unexpectedly appeared at the apical surfaces of CLIC4-suppressed RPE cells, together with a concomitant loss of basal surface expression of monocarboxylate transporter MCT3. Our results suggested that CLIC4 plays an important role in RPE-photoreceptor adhesion, perhaps by modulating the activity of cell surface channels/transporters. We propose that these changes may be attributable to subretinal fluid accumulation in our novel retinal detachment animal model.
16
Alexander, Matthew R., Mike Tyers, Mireille Perret, B. Maureen Craig, Karen S. Fang, and Michael C. Gustin. "Regulation of Cell Cycle Progression by Swe1p and Hog1p Following Hypertonic Stress." Molecular Biology of the Cell 12, no. 1 (January 2001): 53–62. http://dx.doi.org/10.1091/mbc.12.1.53.
Анотація:
Exposure of yeast cells to an increase in external osmolarity induces a temporary growth arrest. Recovery from this stress is mediated by the accumulation of intracellular glycerol and the transcription of several stress response genes. Increased external osmolarity causes a transient accumulation of 1N and 2N cells and a concomitant depletion of S phase cells. Hypertonic stress triggers a cell cycle delay in G2 phase cells that appears distinct from the morphogenesis checkpoint, which operates in early S phase cells. Hypertonic stress causes a decrease in CLB2 mRNA, phosphorylation of Cdc28p, and inhibition of Clb2p-Cdc28p kinase activity, whereas Clb2 protein levels are unaffected. Like the morphogenesis checkpoint, the osmotic stress-induced G2 delay is dependent upon the kinase Swe1p, but is not tightly correlated with inhibition of Clb2p-Cdc28p kinase activity. Thus, deletion ofSWE1 does not prevent the hypertonic stress-induced inhibition of Clb2p-Cdc28p kinase activity. Mutation of the Swe1p phosphorylation site on Cdc28p (Y19) does not fully eliminate the Swe1p-dependent cell cycle delay, suggesting that Swe1p may have functions independent of Cdc28p phosphorylation. Conversely, deletion of the mitogen-activated protein kinase HOG1 does prevent Clb2p-Cdc28p inhibition by hypertonic stress, but does not block Cdc28p phosphorylation or alleviate the cell cycle delay. However, Hog1p does contribute to proper nuclear segregation after hypertonic stress in cells that lack Swe1p. These results suggest a hypertonic stress-induced cell cycle delay in G2 phase that is mediated in a novel way by Swe1p in cooperation with Hog1p.
17
David, Valeriu, Veaceslav Fulga, Vergil Petrovici, Ecaterina Carpenco, and Lilian Saptefrati. "Ang1 immunoexpression vs vascular profile in chorio-villous germinative status in early term compromised pregnancies." Moldovan Medical Journal 66, no. 2 (December 2023): 49–55. http://dx.doi.org/10.52418/moldovan-med-j.66-2.23.08.
Анотація:
Background: A normal maternal-fetal system is essential for the functioning of the placenta during placentation and the establishment of the maternalembryofetal vascular circulation. The angiopoietin/TIE pathway is involved in vascular morphogenesis through regulation, survival and maturation of endothelial cells concomitant with vascular remodeling. Deregulation of pro-angiogenic factor secretion and expression is associated with disruption of vascular morphogenesis, reduction of vascular bed and installation of primary placental insufficiency. The aim: Evaluation of Ang 1 immunoexpression in early term compromised pregnancies in the context of chorio-villary circulatory dysfunction in primary placental insufficiency. Material and methods: Abortion product from 61 patients (stagnant pregnancies – 39 cases, early miscarriage – 8 cases, control group – 14 cases of pregnancies solved on social indications/ desire) were immunohistochemically evaluated with the marker for anti-Ang1 and anti-CD31. Results: The villous syncytiotrophoblast was the most immunoreactive area. Most of cases of the pregnancies terminated on social indications/ desire were anti-Ang1 negative. The levels of anti-Ang1 immunoexpression were statistically significantly different in case of syncytiotrophoblast of early miscarriages and abortions terminated on social indications/ desire. The highest chorio-villous vascular density was noticed in the abortions on social indications/ desire and early misscariages group. Conclusions: The placental period is characterized by a weak angiogenic Ang1 differentiated cellular environment in the chorio-villous germinal site in the group of short term compromised pregnancies. The selectively immunoexpressed cellular profile statistically significantly correlates with placental vascular index and chorio-villous vascular density in stagnant pregnancies.
18
Kim, Dong-Kyu, Ju Ang Kim, Joosang Park, Ava Niazi, Ali Almishaal та Sungjin Park. "The release of surface-anchored α-tectorin, an apical extracellular matrix protein, mediates tectorial membrane organization". Science Advances 5, № 11 (листопад 2019): eaay6300. http://dx.doi.org/10.1126/sciadv.aay6300.
Анотація:
The tectorial membrane (TM) is an apical extracellular matrix (ECM) that hovers over the cochlear sensory epithelium and plays an essential role in auditory transduction. The TM forms facing the luminal endolymph-filled space and exhibits complex ultrastructure. Contrary to the current extracellular assembly model, which posits that secreted collagen fibrils and ECM components self-arrange in the extracellular space, we show that surface tethering of α-tectorin (TECTA) via a glycosylphosphatidylinositol anchor is essential to prevent diffusion of secreted TM components. In the absence of surface-tethered TECTA, collagen fibrils aggregate randomly and fail to recruit TM glycoproteins. Conversely, conversion of TECTA into a transmembrane form results in a layer of collagens on the epithelial surface that fails to form a multilayered structure. We propose a three-dimensional printing model for TM morphogenesis: A new layer of ECM is printed on the cell surface concomitant with the release of a preestablished layer to generate the multilayered TM.
19
Andrés, Germán, Alí Alejo, José Salas, and María L. Salas. "African Swine Fever Virus Polyproteins pp220 and pp62 Assemble into the Core Shell." Journal of Virology 76, no. 24 (December 15, 2002): 12473–82. http://dx.doi.org/10.1128/jvi.76.24.12473-12482.2002.
Анотація:
ABSTRACT African swine fever virus (ASFV), a complex enveloped DNA virus, expresses two polyprotein precursors, pp220 and pp62, which after proteolytic processing give rise to several major components of the virus particle. We have analyzed the structural role of polyprotein pp62, the precursor form of mature products p35 and p15, in virus morphogenesis. Densitometric analysis of one- and two-dimensional gels of purified virions showed that proteins p35 and p15, as well as the pp220-derived products, are present in equimolecular amounts in the virus particle. Immunoelectron microscopy revealed that the pp62-derived products localize at the core shell, a matrix-like domain placed between the DNA-containing nucleoid and the inner envelope, where the pp220-derived products are also localized. Pulse-chase experiments indicated that the processing of both polyprotein precursors is concomitant with virus assembly. Furthermore, using inducible ASFV recombinants, we show that pp62 processing requires the expression of the pp220 core precursor, whereas the processing of both precursors pp220 and pp62 is dependent on expression of the major capsid protein p72. Interestingly, when p72 expression is blocked, unprocessed pp220 and pp62 polyproteins assemble into aberrant zipper-like elements consisting of an elongated membrane-bound protein structure reminiscent of the core shell. Moreover, the two polyproteins, when coexpressed in COS cells, interact with each other to form zipper-like structures. Together, these findings indicate that the mature products derived from both polyproteins, which collectively account for about 30% of the virion protein mass, are the basic components of the core shell and that polyprotein processing represents a maturational process related to ASFV morphogenesis.
20
Nash, Evelyn E., Brian M. Peters, Glen E. Palmer, Paul L. Fidel, and Mairi C. Noverr. "Morphogenesis Is Not Required for Candida albicans-Staphylococcus aureus Intra-Abdominal Infection-Mediated Dissemination and Lethal Sepsis." Infection and Immunity 82, no. 8 (June 2, 2014): 3426–35. http://dx.doi.org/10.1128/iai.01746-14.
Анотація:
ABSTRACTIntra-abdominal polymicrobial infections cause significant morbidity and mortality. An established experimental mouse model ofStaphylococcus aureus-Candida albicansintra-abdominal infection results in ∼60% mortality within 48 h postinoculation, concomitant with amplified local inflammatory responses, while monomicrobial infections are avirulent. The purpose of this study was to characterize early local and systemic innate responses during coinfection and determine the role ofC. albicansmorphogenesis in lethality, a trait involved in virulence and physical interaction withS. aureus. Local and systemic proinflammatory cytokines were significantly elevated during coinfection at early time points (4 to 12 h) compared to those in monoinfection. In contrast, microbial burdens in the organs and peritoneal lavage fluid were similar between mono- and coinfected animals through 24 h, as was peritoneal neutrophil infiltration. After optimizing the model for 100% mortality within 48 h, using 3.5 × 107C. albicans(5× increase), coinfection withC. albicansyeast-locked or hypha-locked mutants showed similar mortality, dissemination, and local and systemic inflammation to the isogenic control. However, coinfection with the yeast-lockedC. albicansmutant given intravenously (i.v.) andS. aureusgiven intraperitoneally (i.p.) failed to induce mortality. These results suggest a unique intra-abdominal interaction between the host andC. albicans-S. aureusthat results in strong inflammatory responses, dissemination, and lethal sepsis, independent ofC. albicansmorphogenesis.
21
Fleury, Graziela, Bruno G. Ferreira, Geraldo L. G. Soares, Denis C. Oliveira, and Rosy M. S. Isaias. "Elucidating the determination of the rosette galls induced by Pisphondylia brasiliensis Couri and Maia 1992 (Cecidomyiidae) on Guapira opposita (Nyctaginaceae)." Australian Journal of Botany 63, no. 7 (2015): 608. http://dx.doi.org/10.1071/bt15106.
Анотація:
The modulation of plant development has been the focus of research on insect galls because galling insects induce distinct shapes to acquire the same necessities, shelter and food. Due to the variety of gall morphotypes, it can be assumed that the key processes for their development rely on plant cells’ morphogenetical potentialities. In the present study we investigated the rosette bud galls induced by Pisphondylia brasiliensis on Guapira opposita to check whether two morphogenetical pathways – the shortening of the internodes and the over differentiation of axillary buds – are independent or whether they are concomitant events towards the morphogenesis of the galls. Biometrical measures were made to test whether the final size of the galls is correlated with the number of inducers per gall. We noted that two patterns of activity were observed in gall meristems: the first differentiated pairs of leaves with opposite phyllotaxy, and the other differentiated new buds at the base of each leafy projection, with the development of sequential leafy projections, in a disorganised phyllotaxy. This second pattern repeated until gall maturation, when a master cambium, typical of the Nyctaginaceae, differentiated in larger galls. The two morphogenetical pathways occurred concomitantly, leading to the overproduction of leafy projections. Cell responses at gall development site produce mechanical protection to P. brasiliensis individuals. The larger galls have the higher number of inducers, and the coalescence of galls allows an increase in gall size by precociously triggering the master cambium activity, a developmental peculiarity of G. opposita uncommon for Cecidomyiidae galls.
22
Frago, L. M., Y. Leon, E. J. de la Rosa, A. Gomez-Munoz, and I. Varela-Nieto. "Nerve growth factor and ceramides modulate cell death in the early developing inner ear." Journal of Cell Science 111, no. 5 (March 1, 1998): 549–56. http://dx.doi.org/10.1242/jcs.111.5.549.
Анотація:
Regulation of normal development involves a dynamic balance of the mechanisms regulating cell division, differentiation and death. We have investigated the signalling mechanisms involved in regulation of the balance between cell proliferation and apoptotic cell death in the otic vesicle. The sphingomyelin pathway signals apoptosis for nerve growth factor upon binding to p75 receptors. It is initiated by sphingomyelin hydrolysis to generate the second messenger ceramide. In the present study, we show that nerve growth factor stimulates sphingomyelin hydrolysis and the concomitant ceramide release in organotypic cultures of otic vesicles. Both nerve growth factor and ceramide induce apoptotic responses to a different extent. Ceramide-induced apoptosis was suppressed by insulin-like growth factor-I which is a strong promoter of cell growth and morphogenesis for the developing inner ear. In contrast, ceramide-1-phosphate protected the explants from apoptosis induced by serum withdrawal but did not antagonise ceramide-induced cell death. This study suggests that sphingomyelin-derived second messengers might be key modulators of programmed cell death during development.
23
Shi, Jiejun, Meizhu Zheng, Youqiong Ye, Min Li, Xiaolong Chen, Xinjie Hu, Jin Sun, Xiaobai Zhang, and Cizhong Jiang. "Drosophila Brahma complex remodels nucleosome organizations in multiple aspects." Nucleic Acids Research 42, no. 15 (July 31, 2014): 9730–39. http://dx.doi.org/10.1093/nar/gku717.
Анотація:
Abstract ATP-dependent chromatin remodeling complexes regulate nucleosome organizations. In Drosophila, gene Brm encodes the core Brahma complex, the ATPase subunit of SWI/SNF class of chromatin remodelers. Its role in modulating the nucleosome landscape in vivo is unclear. In this study, we knocked down Brm in Drosophila third instar larvae to explore the changes in nucleosome profiles and global gene transcription. The results show that Brm knockdown leads to nucleosome occupancy changes throughout the entire genome with a bias in occupancy decrease. In contrast, the knockdown has limited impacts on nucleosome position shift. The knockdown also alters another important physical property of nucleosome positioning, fuzziness. Nucleosome position shift, gain or loss and fuzziness changes are all enriched in promoter regions. Nucleosome arrays around the 5′ ends of genes are reorganized in five patterns as a result of Brm knockdown. Intriguingly, the concomitant changes in the genes adjacent to the Brahma-dependent remodeling regions have important roles in development and morphogenesis. Further analyses reveal abundance of AT-rich motifs for transcription factors in the remodeling regions.
24
Dressler, Simone, Philipp Meyer-Marcotty, Nicole Weisschuh, Anahita Jablonski-Momeni, Klaus Pieper, Gwendolyn Gramer, and Eugen Gramer. "Dental and Craniofacial Anomalies Associated with Axenfeld-Rieger Syndrome with PITX2 Mutation." Case Reports in Medicine 2010 (2010): 1–7. http://dx.doi.org/10.1155/2010/621984.
Анотація:
Axenfeld-Rieger syndrome (ARS) (OMIM Nr.: 180500) is a rare autosomal dominant disorder (1 : 200000) with genetic and morphologic variability. Glaucoma is associated in 50% of the patients. Craniofacial and dental anomalies are frequently reported with ARS. The present study was designed as a multidisciplinary analysis of orthodontic, ophthalmologic, and genotypical features. A three-generation pedigree was ascertained through a family with ARS. Clinically, radiographic and genetic analyses were performed. Despite an identical genotype in all patients, the phenotype varies in expressivity of craniofacial and dental morphology. Screening for PITX2 and FOXC1 mutations by direct DNA-sequencing revealed a P64L missense mutation in PITX2 in all family members, supporting earlier reports that PITX2 is an essential factor in morphogenesis of teeth and craniofacial skeleton. Despite the fact that the family members had identical mutations, morphologic differences were evident. The concomitant occurrence of rare dental and craniofacial anomalies may be early diagnostic indications of ARS. Early detection of ARS and elevated intraocular pressure (IOP) helps to prevent visual field loss.
25
Vernay, Aurélia, Sébastien Schaub, Isabelle Guillas, Martine Bassilana, and Robert A. Arkowitz. "A steep phosphoinositide bis-phosphate gradient forms during fungal filamentous growth." Journal of Cell Biology 198, no. 4 (August 13, 2012): 711–30. http://dx.doi.org/10.1083/jcb.201203099.
Анотація:
Membrane lipids have been implicated in many critical cellular processes, yet little is known about the role of asymmetric lipid distribution in cell morphogenesis. The phosphoinositide bis-phosphate PI(4,5)P2 is essential for polarized growth in a range of organisms. Although an asymmetric distribution of this phospholipid has been observed in some cells, long-range gradients of PI(4,5)P2 have not been observed. Here, we show that in the human pathogenic fungus Candida albicans a steep, long-range gradient of PI(4,5)P2 occurs concomitant with emergence of the hyphal filament. Both sufficient PI(4)P synthesis and the actin cytoskeleton are necessary for this steep PI(4,5)P2 gradient. In contrast, neither microtubules nor asymmetrically localized mRNAs are critical. Our results indicate that a gradient of PI(4,5)P2, crucial for filamentous growth, is generated and maintained by the filament tip–localized PI(4)P-5-kinase Mss4 and clearing of this lipid at the back of the cell. Furthermore, we propose that slow membrane diffusion of PI(4,5)P2 contributes to the maintenance of such a gradient.
26
Goldstein, R. S., and C. Kalcheim. "Normal segmentation and size of the primary sympathetic ganglia depend upon the alternation of rostrocaudal properties of the somites." Development 112, no. 1 (May 1, 1991): 327–34. http://dx.doi.org/10.1242/dev.112.1.327.
Анотація:
Metameric organization of the dorsal root ganglia (DRG) and ventral roots depends on the alternation of rostrocaudal properties within the somites. In addition, the size of DRG is likely to be regulated by the adjacent mesoderm, because unilateral creation of a paraxial mesoderm with only rostral somitic (RS) halves, leads to the development of non-segmented DRG that are larger and contain more cells than the sum of the contralateral, control DRG. We have now extended our studies of the role of the paraxial mesoderm in the morphogenesis of the peripheral nervous system (PNS) to another metameric PNS component, the sympathetic ganglia (SG). The development of the primary sympathetic chain was studied in chick-quail chimeras with multiple half-somite grafts using quantitative morphometric analysis. In the presence of an exclusively rostral or caudal somitic mesoderm, segmentation of the initially homogeneous primary sympathetic chain into ganglia is prevented. Therefore, the SG, like the DRG and ventral roots, require the normal rostrocaudal alternation of the somitic mesoderm for segmental morphogenesis. On embryonic day 4 (E4), there is a 38% average decrease in the volume of the primary sympathetic chain opposite a RS mesoderm, compared with the primary chain on the unoperated side. This is in contrast to the average increase of 27% in the volume of the DRG opposite the grafted mesoderm in the same embryos. Our results, and classical observations, have led us to propose a model in which the mesoderm controls DRG and SG size by modulating the partition of migrating NC precursors between the anlage of these two ganglion types. According to this model, the reduction in SG volume and concomitant increase in DRG volume observed opposite RS grafts, results from the arrest in the DRG anlage of neural crest cells that normally migrate to the SG.
27
Xu, J., H. Liu, Y. Lan, J. S. Park, and R. Jiang. "Genome-wide Identification of Foxf2 Target Genes in Palate Development." Journal of Dental Research 99, no. 4 (February 10, 2020): 463–71. http://dx.doi.org/10.1177/0022034520904018.
Анотація:
Cleft palate is among the most common structural birth defects in humans. Previous studies have shown that mutations in FOXF2 are associated with cleft palate in humans and mice and that Foxf2 acts in a Shh-Foxf-Fgf18-Shh molecular network controlling palatal shelf growth. In this study, we combined RNA-seq and ChIP-seq approaches to identify direct transcriptional target genes mediating Foxf2 function in palate development in mice. Of 155 genes that exhibited Foxf2-dependent expression in the developing palatal mesenchyme, 88 contained or were located next to Foxf2-binding sites. Through in situ hybridization analyses, we demonstrate that expression of many of these target genes, including multiple genes encoding transcription factors and several encoding extracellular matrix–modifying proteins, were specifically upregulated in the posterior region of palatal shelves in Foxf2-/- mouse embryos. Foxf2 occupancy at many of these putative target loci, including Fgf18, in the developing palatal tissues was verified by ChIP–polymerase chain reaction analyses. One of the Foxf2 target genes, Chst2, encodes a carbohydrate sulfotransferase integral to glycosaminoglycan sulfation. Correlating with ectopic Chst2 expression, Foxf2-/- embryos a exhibited region-specific increase in sulfated keratan sulfate and a concomitant reduction in chondroitin sulfate accumulation in the posterior palatal mesenchyme. However, expression of the core protein of versican, a major chondroitin sulfate proteoglycan important in palatal shelf morphogenesis, was increased, whereas expression of collagen I was reduced in the corresponding region of the palatal mesenchyme. These results indicate that, in addition to regulating palatal shelf growth through the Fgf18-Shh signaling network, Foxf2 controls palatal shelf morphogenesis through regulating expression of multiple transcription factors as well as through directly controlling the synthesis and processing of extracellular matrix components in the palatal mesenchyme. Our ChIP-seq and RNA-seq data sets provide an excellent resource for comprehensive understanding of the molecular network controlling palate development.
28
Chen, Weihao, Fengyan Meng, Xianyin Zeng, Xiaohan Cao, Guixian Bu, Xiaogang Du, Guozhi Yu, et al. "Mechanic Insight into the Distinct and Common Roles of Ovariectomy Versus Adrenalectomy on Adipose Tissue Remodeling in Female Mice." International Journal of Molecular Sciences 24, no. 3 (January 24, 2023): 2308. http://dx.doi.org/10.3390/ijms24032308.
Анотація:
Dysfunctions of the ovaries and adrenal glands are both evidenced to cause aberrant adipose tissue (AT) remodeling and resultant metabolic disorders, but their distinct and common roles are poorly understood. In this study, through biochemical, histological and RNA-seq analyses, we comprehensively explored the mechanisms underpinning subcutaneous (SAT) and visceral adipose tissue (VAT) remodeling, in response to ovariectomy (OVX) versus adrenalectomy (ADX) in female mice. OVX promoted adipocyte differentiation and fat accumulation in both SAT and VAT, by potentiating the Pparg signaling, while ADX universally prevented the cell proliferation and extracellular matrix organization in both SAT and VAT, likely by inactivating the Nr3c1 signaling, thus causing lipoatrophy in females. ADX, but not OVX, exerted great effects on the intrinsic difference between SAT and VAT. Specifically, ADX reversed a large cluster of genes differentially expressed between SAT and VAT, by activating 12 key transcription factors, and thereby caused senescent cell accumulation, massive B cell infiltration and the development of selective inflammatory response in SAT. Commonly, both OVX and ADX enhance circadian rhythmicity in VAT, and impair cell proliferation, neurogenesis, tissue morphogenesis, as well as extracellular matrix organization in SAT, thus causing dysfunction of adipose tissues and concomitant metabolic disorders.
29
Schramek, Herbert, Elisabeth Feifel, Ingrid Marschitz, Nadejda Golochtchapova, Gerhard Gstraunthaler, and Roberto Montesano. "Loss of active MEK1-ERK1/2 restores epithelial phenotype and morphogenesis in transdifferentiated MDCK cells." American Journal of Physiology-Cell Physiology 285, no. 3 (September 2003): C652—C661. http://dx.doi.org/10.1152/ajpcell.00463.2002.
Анотація:
Constitutive activation of the MAPK/ERK kinase (MEK)1-ERK2 signaling module in Madin-Darby canine kidney (MDCK)-C7 cells disrupts their ability to form cystlike structures in collagen gels and induces an invasive, myofibroblastlike phenotype. However, the reversibility of these cellular events, as well as the relative role of both MEK isoforms (MEK1 and MEK2) and both ERK isoforms (ERK1 and ERK2) during these processes, has not yet been investigated. We now report that loss of constitutively active MEK1 (caMEK1) and, thus, loss of active ERK1/2 in C7caMEK1 cells is associated with increased MEK2 protein expression, reexpression of ERK1 protein, and epithelial redifferentiation of these cells. The morphological changes toward an epithelial phenotype in these revertant cell lines (C7rev4, C7rev5, C7rev7) are reflected by the upregulation of epithelial marker proteins, such as E-cadherin, β-catenin, and cytokeratin, by the loss of α-smooth muscle actin expression, and by the ability of these epithelial revertants to form well-organized spherical cysts when grown in three-dimensional collagen gels. Further evidence for a role of the MEK1-ERK1/2 module in epithelial-mesenchymal transition was obtained from the analysis of two novel, spontaneously transdifferentiated MDCK-C7 cell clones (C7e1 and C7e2 cells). In these clones, increased MEK1/2-ERK1/2 phosphorylation, reduced MEK2 protein expression, and loss of ERK1 protein expression is associated with phenotypic alterations similar to those observed in transdifferentiated C7caMEK1 cells. C7e1 cells at least partially regained some of their epithelial characteristics at higher passages. In contrast, C7e2 cells maintained a transdifferentiated phenotype at high passage, were unable to generate cystlike epithelial structures, and retained invasive properties when grown on a three-dimensional collagen matrix. We conclude that in renal epithelial MDCK-C7 cells, stable epithelial-to-mesenchymal transition (EMT) is associated with loss of ERK1 protein expression, reduced MEK2 protein expression, and increased basal ERK2 phosphorylation. In contrast, loss of active MEK1-ERK1/2 results in increased MEK2 protein expression and reexpression of ERK1 protein, concomitant with the restoration of epithelial phenotype and the ability to form cystic structures.
30
Chen, W. T., J. M. Chen, and S. C. Mueller. "Coupled expression and colocalization of 140K cell adhesion molecules, fibronectin, and laminin during morphogenesis and cytodifferentiation of chick lung cells." Journal of Cell Biology 103, no. 3 (September 1, 1986): 1073–90. http://dx.doi.org/10.1083/jcb.103.3.1073.
Анотація:
We have analyzed the expression and distribution of fibronectin, laminin, and the 140K cell adhesion molecules (140K complex) in embryonic chick lung cells by a combination of biochemical and immunofluorescent approaches. The 140K complex was identified by monoclonal antibody JG22E as a complex of glycoproteins averaging 140,000 Mr and has been implicated in vitro as a receptor for fibronectin and laminin. Our studies provide the first description that the 140K complex is developmentally regulated, and that the 140K complex appears to be involved in adhesion of epithelial and endothelial cells during morphogenesis. We have shown that the 140K complex is expressed in high quantity in embryonic lung cell types, but is markedly reduced in all of the differentiated cell types except smooth muscle. Embryonic lung cells are enriched in 140K complex on portions of cells in close proximity to areas rich in fibronectin. For example, during the formation of airways and alveolar tissues, 140K complex is concentrated at the basal surfaces of epithelial cells adjacent to fibronectin. Likewise, during the angiogenic invasion of capillaries into lung mesenchyme, the 140K complex becomes localized at sites on the basal surfaces of endothelial cells in close contact with fibronectin. Finally, cytodifferentiating lung smooth muscle cells show unusually high levels of 140K complex, fibronectin, and laminin that persist into the adult. In contrast to fibronectin, laminin is found to be uniformly distributed in the basement membranes of differentiating epithelial cells. It becomes prominent in adult alveolar epithelium and airway epithelium concomitant with a reduction or loss of 140K complex and fibronectin at cell-basement membrane attachment sites. Surprisingly, laminin is also present in a punctate pattern in the mesenchyme of early lung buds, however, laminin, fibronectin, and 140K complex are greatly reduced or lost during mesenchymal maturation. Our results are consistent with the active participation of the 140K complex in cell-to-matrix adhesion during morphogenesis of alveolar walls and cytodifferentiation of mesenchymal and smooth muscle cells.
31
Deleuze, Virginie, Elias Chalhoub, Rawan El-Hajj, Christiane Dohet, Mikael Le Clech, Philippe Huber, and Daniele Mathieu. "The Basic Helix-Loop-Helix TAL1/SCL and Its Partners E47 and LMO2 Act Upstream of the VE-Cadherin Gene in Endothelial Cells." Blood 108, no. 11 (November 16, 2006): 1795. http://dx.doi.org/10.1182/blood.v108.11.1795.1795.
Анотація:
Abstract The basic helix-loop-helix protein TAL-1/SCL, essential for the formation of the hematopoietic system, is also required for vascular development and more particularly for embryonic angiogenesis. We previously reported that TAL-1 acts as a positive factor for post-natal angiogenesis by stimulating endothelial morphogenesis. To understand how TAL-1 modulates angiogenesis, we investigated the functional consequences of TAL-1 silencing, mediated by small-interfering RNAs, in human primary endothelial cells (ECs). We found that TAL-1 knockdown impaired in vitro EC tubulomorphogenesis (in 2-D on Matrigel or 3-D in collagen I gel), with the notable absence of cell-cell contacts, a prerequisite for morphogenesis initiation. This cellular deficiency was associated with a dramatic reduction in the vascular-endothelial (VE)-cadherin at intercellular junctions, the major component of endothelial adherens junctions. In contrast, PECAM (or CD31) was present at cell-cell junctions at the same levels as control cells. Importantly, silencing of two known TAL-1-partners in hematopoietic cells, E47 or LMO2, produce the same effects as TAL-1. Accordingly, silencing of TAL-1, as well as E47 and LMO2, provoked down-regulation of VE-cadherin at both the mRNA and protein levels. Transient transfection experiments in HUVECs showed that TAL-1 and E47 regulate the VE-cadherin promoter through a specialized E-box element. Finally, endogenous VE-cadherin transcription could be directly activated in non-endothelial HEK-293 cells that neither express TAL-1 or LMO2, by the sole concomitant ectopic expression of TAL-1, E47 and LMO2. Overall, our data demonstrate that a multiprotein complex containing at least TAL-1, LMO2 and E47 act upstream of the VE-cadherin gene. We are currently performing chromatin immunoprecipitation (ChIP) to investigate whether the TAL-1-containing complex binds in vivo the VE-cadherin promoter. This study identifies VE-cadherin as an upstream TAL-1-target gene in the endothelial lineage, and provides a first clue in TAL-1 function in the control of angiogenesis.
32
Fuchs, Walter, Harald Granzow, Barbara G. Klupp, Martina Kopp, and Thomas C. Mettenleiter. "The UL48 Tegument Protein of Pseudorabies Virus Is Critical for Intracytoplasmic Assembly of Infectious Virions." Journal of Virology 76, no. 13 (July 1, 2002): 6729–42. http://dx.doi.org/10.1128/jvi.76.13.6729-6742.2002.
Анотація:
ABSTRACT The pseudorabies virus (PrV) homolog of the tegument protein encoded by the UL48 gene of herpes simplex virus type 1 (HSV-1) was identified by using a monospecific rabbit antiserum against a bacterial fusion protein. UL48-related polypeptides of 53, 55, and 57 kDa were detected in Western blots of infected cells and purified virions. Immunofluorescence studies demonstrated that the PrV UL48 protein is predominantly localized in the cytoplasm but is also found in the nuclei of infected cells. Moreover, it is a constituent of extracellular virus particles but is absent from primary enveloped perinuclear virions. In noncomplementing cells, a UL48-negative PrV mutant (PrV-ΔUL48) exhibited delayed growth and significantly reduced plaque sizes and virus titers, deficiencies which were corrected in UL48-expressing cells. RNA analyses indicated that, like its HSV-1 homolog, the PrV UL48 protein is involved in regulation of immediate-early gene expression. However, the most salient effect of the UL48 gene deletion was a severe defect in virion morphogenesis. Late after infection, electron microscopy of cells infected with PrV-ΔUL48 revealed retention of newly formed nucleocapsids in the cytoplasm, whereas enveloped intracytoplasmic or extracellular complete virions were only rarely observed. In contrast, capsidless particles were produced and released in great amounts. Remarkably, the intracytoplasmic capsids were labeled with antibodies against the UL36 and UL37 tegument proteins, whereas the capsidless particles were labeled with antisera directed against the UL46, UL47, and UL49 tegument proteins. These findings suggested that the UL48 protein is involved in linking capsid and future envelope-associated tegument proteins during virion formation. Thus, like its HSV-1 homolog, the UL48 protein of PrV functions in at least two different steps of the viral life cycle. The drastic inhibition of virion formation in the absence of the PrV UL48 protein indicates that it plays an important role in virion morphogenesis prior to secondary envelopment of intracytoplasmic nucleocapsids. However, the UL48 gene of PrV is not absolutely essential, and concomitant deletion of the adjacent tegument protein gene UL49 also did not abolish virus replication in cell culture.
33
Modak, Sohan Prabhakar. "Cell population growth regulates dorsalization and caudalization during chick morphogenesis and programmed cell death in lens fibres." International Journal of Developmental Biology 64, no. 1-2-3 (2020): 45–57. http://dx.doi.org/10.1387/ijdb.190270sm.
Анотація:
The chick embryo ectoblast was examined for a possible relationship between the state of neural competence and cell population growth. It was found that although ectoblast cells with doubling times ranging between 5 to 20 h exhibit neural competence, the extent of neutralization induced by the Hensen’s node depends on the duration of the cell cycle; the longer the doubling time of the competent ectoblast, the stronger the induction and the greater the induced neural tissue. Neural induction in the competent ectoblast occurs in at least two steps: the first lasts for 1-2 h of direct contact with the inducing Hensen’s node graft; a contact for another 2 h with even a non-inducing post-nodal fragment is essential to consolidate neutralization. Hensen’s node graft induces mitotic activity in the competent ectoblast in contact. Teratogens which inhibit cell population growth, development and blastoderm expansion in chick embryo gastrula cause concomitant caudalization of the embryonic axis. We confirm Yamada’s hypothesis that dorsalization is under positive mitogenic control, whereas caudalization is controlled by a negative cell cycle regulation. Reverse transcripts of chick gastrula mRNA were cloned in pBR322. Colony hybridization with cDNA made against chicken yolk RNA showed positive clones. Thus chicken yolk contains maternal mRNAs. cDNA made against mRNA extracted from stage 10 foreheads was hybridized with RNA from stage 1 to 13 embryos, 19 day lens and egg yolk. The hybridization signal, which was low between stages 1 to 7, increased between stages 10-13 and decreased thereafter. Forehead cDNA also hybridized to yolk RNA. Thus, maternal RNA sequences are present in the early chick embryo. During lens development, epithelial cells retain proliferative activity and their progeny reaching a stationary phase join the fibre area and contribute to the growth of fibre cells. The rate of transfer from epithelium to fibre regulates the rate of programmed cell death of the non-dividing differentiated lens fibre cells.
34
Kimata, Koji, Teruyo Sakakura, Yutaka Inaguma, Masato Kato, and Yasuaki Nishizuka. "Participation of two different mesenchymes in the developing mouse mammary gland: synthesis of basement membrane components by fat pad precursor cells." Development 89, no. 1 (October 1, 1985): 243–57. http://dx.doi.org/10.1242/dev.89.1.243.
Анотація:
Two different types of mesenchyme, fat pad precursor cells (FP) and fibroblastic cells (MM) are involved in the morphogenesis of mammary gland epithelium of mouse embryo. Especially, an interaction between FP and the epithelium is necessary for its characteristic shaping of ductal branching structure. To assess the relative participations of the mesenchymes, we have analysed the extracellular matrix products by immunofluorescent staining method using antibodies to laminin, proteoheparan sulphate, and fibronectin. The staining patterns suggested that, after the 16th day of gestation when fatty substances first appeared in FP and the epithelial rudiments started to elongate and branch rapidly, FP initiated synthesis of laminin and proteoheparan sulphate, while MM synthesized fibronectin at all times. Attention was also paid to differences in the epithelial basement membranes (BM) concomitant with ones in the mesenchyme. BM were always stained with antibodies to laminin and proteoheparan sulphate. However, topographical differences in thickness were observed: the one facing FP, often seen at the tip region of the end bud, was thin, while the other surrounded by MM, often at the flank region of the duct, was thick. Specific elaboration of BM-like extracellular matrix products by FP may attribute to observed differences in BM thickness which are related to the characteristic shaping of the mammary gland.
35
Greenwel, Patricia, Shizuko Tanaka, Dmitri Penkov, Wen Zhang, Michelle Olive, Jonathan Moll, Charles Vinson, Maurizio Di Liberto, and Francesco Ramirez. "Tumor Necrosis Factor Alpha Inhibits Type I Collagen Synthesis through Repressive CCAAT/Enhancer-Binding Proteins." Molecular and Cellular Biology 20, no. 3 (February 1, 2000): 912–18. http://dx.doi.org/10.1128/mcb.20.3.912-918.2000.
Анотація:
ABSTRACT Extracellular matrix (ECM) formation and remodeling are critical processes for proper morphogenesis, organogenesis, and tissue repair. The proinflammatory cytokine tumor necrosis factor alpha (TNF-α) inhibits ECM accumulation by stimulating the expression of matrix proteolytic enzymes and by downregulating the deposition of structural macromolecules such as type I collagen. Stimulation of ECM degradation has been linked to prolonged activation of jun gene expression by the cytokine. Here we demonstrate that TNF-α inhibits transcription of the gene coding for the α2 chain of type I collagen [α2(I) collagen] in cultured fibroblasts by stimulating the synthesis and binding of repressive CCAAT/enhancer proteins (C/EBPs) to a previously identified TNF-α-responsive element. This conclusion was based on the concomitant identification of C/EBPβ and C/EBPδ as TNF-α-induced factors by biochemical purification and expression library screening. It was further supported by the ability of the C/EBP-specific dominant-negative (DN) protein to block TNF-α inhibition of α2(I) collagen but not TNF-α stimulation of the MMP-13 protease. The DN protein also blocked TNF-α downregulation of the gene coding for the α1 chain of type I collagen. The study therefore implicates repressive C/EBPs in the TNF-α-induced signaling pathway that controls ECM formation and remodeling.
36
Huang, Qiong, and Nader Sheibani. "High glucose promotes retinal endothelial cell migration through activation of Src, PI3K/Akt1/eNOS, and ERKs." American Journal of Physiology-Cell Physiology 295, no. 6 (December 2008): C1647—C1657. http://dx.doi.org/10.1152/ajpcell.00322.2008.
Анотація:
Hyperglycemia impacts retinal vascular function and promotes the development and progression of diabetic retinopathy, which ultimately results in growth of new blood vessels and loss of vision. How high glucose affects retinal endothelial cell (EC) properties requires further investigation. Here we determined the impact of high glucose on mouse retinal EC function in vitro. High glucose significantly enhanced the migration of retinal EC without impacting their proliferation, apoptosis, adhesion, and capillary morphogenesis. The enhanced migration of retinal EC under high glucose was reversed in the presence of the antioxidant N-acetylcysteine, suggesting increased oxidative stress under high-glucose conditions. Retinal EC under high-glucose conditions also expressed increased levels of fibronectin, osteopontin, and αvβ3-integrin, and reduced levels of thrombospondin-1. These changes were concomitant with sustained activation of the downstream prosurvival and promigratory signaling pathways, including Src kinase, phosphatidylinositol 3-kinase/Akt1/endothelial nitric oxide synthase, and ERKs. The sustained activation of these signaling pathways was essential for enhanced migration of retinal EC under high-glucose conditions. Together, our results indicate the exposure of retinal EC to high glucose promotes a promigratory phenotype. Thus alterations in the proangiogenic properties of retinal EC during diabetes may contribute to the development and pathogenesis of diabetic retinopathy.
37
Apte, Udayan, Gang Zeng, Michael D. Thompson, Peggy Muller, Amanda Micsenyi, Benjamin Cieply, Klaus H. Kaestner та Satdarshan P. S. Monga. "β-Catenin is critical for early postnatal liver growth". American Journal of Physiology-Gastrointestinal and Liver Physiology 292, № 6 (червень 2007): G1578—G1585. http://dx.doi.org/10.1152/ajpgi.00359.2006.
Анотація:
The Wnt/β-catenin pathway plays an important role in embryonic liver development, morphogenesis, and organogenesis. Here, we report on the activation of β-catenin during early postnatal liver growth. Modulation of β-catenin expression was studied in CD-1 mice livers over a time course of 0 to 30 postnatal days (PD) and 3 mo. Increases in total and active β-catenin were observed in developing livers from PD 5 to 20. A concomitant increase in the β-catenin-transcription factor (TCF) complex along with nuclear and cytoplasmic β-catenin was also evident, which coincided with ongoing hepatocyte proliferation by PCNA immunohistochemistry. This activation of β-catenin was multifactorial, including cyclical inhibition of glycogen synthase kinase-3β, suppression of casein kinase-IIα, and a transient increase in β-catenin gene expression. Coprecipitation experiments revealed the formation of the β-catenin-cadherin complex at PD 5, whereas adequate β-catenin-c-Met complex at the hepatocyte membrane did not form until PD 20, which might be contributing to the free β-catenin pool during early postnatal growth. Furthermore, β-catenin liver-specific knockout mice exhibited smaller livers at PD 30, secondary to diminished hepatocyte proliferation. These data indicate that the activation of β-catenin is critical for early postnatal liver growth and development.
38
Sawhney, Ravi K., and Jonathon Howard. "Slow local movements of collagen fibers by fibroblasts drive the rapid global self-organization of collagen gels." Journal of Cell Biology 157, no. 6 (June 10, 2002): 1083–92. http://dx.doi.org/10.1083/jcb.200203069.
Анотація:
Aclassic model for tissue morphogenesis is the formation of ligament-like straps between explants of fibroblasts placed in collagen gels. The patterns arise from mechanical forces exerted by cells on their substrates (Harris et al., 1981). However, where do such straps come from, and how are slow local movements of cells transduced into dramatic long-distance redistributions of collagen? We embedded primary mouse skin and human periodontal ligament fibroblasts in collagen gels and measured the time course of patterning by using a novel computer algorithm to calculate anisotropy, and by tracking glass beads dispersed in the gel. As fibroblasts began to spread into their immediate environments, a coordinated rearrangement of collagen commenced throughout the gel, producing a strap on a time scale of minutes. Killing of cells afterwards resulted in a partial relaxation of the matrix strain. Surprisingly, relatively small movements of collagen molecules on the tensile axis between two pulling explants induced a much larger concomitant compression of the gel perpendicular to the axis, organizing and aligning fibers into a strap. We propose that this amplification is due to the geometry of the collagen matrix, and that analogous amplified movements may drive morphological changes in other biological meshes, both outside and inside the cell.
39
Pujuguet, Philippe, Laurence Del Maestro, Alexis Gautreau, Daniel Louvard, and Monique Arpin. "Ezrin Regulates E-Cadherin-dependent Adherens Junction Assembly through Rac1 Activation." Molecular Biology of the Cell 14, no. 5 (May 2003): 2181–91. http://dx.doi.org/10.1091/mbc.e02-07-0410.
Анотація:
Ezrin, a membrane cytoskeleton linker, is involved in cellular functions, including epithelial cell morphogenesis and adhesion. A mutant form of ezrin, ezrin T567D, maintains the protein in an open conformation, which when expressed in Madin-Darby canine kidney cells causes extensive formation of lamellipodia and altered cell-cell contacts at low cell density. Furthermore, these cells do not form tubules when grown in a collagen type I matrix. While measuring the activity of Rho family GTPases, we found that Rac1, but not RhoA or Cdc 42, is activated in ezrin T567D-expressing cells, compared with cells expressing wild-type ezrin. Together with Rac1 activation, we observed an accumulation of E-cadherin in intracellular compartments and a concomitant decrease in the level of E-cadherin present at the plasma membrane. This effect could be reversed with a dominant negative form of Rac1, N17Rac1. We show that after a calcium switch, the delivery of E-cadherin from an internalized pool to the plasma membrane is greatly delayed in ezrin T567D-producing cells. In confluent cells, ezrin T567D production decreases the rate of E-cadherin internalization. Our results identify a new role for ezrin in cell adhesion through the activation of the GTPase Rac1 and the trafficking of E-cadherin to the plasma membrane.
40
Di Domenico, Marina, Melanie Jokwitz, Walter Witke, and Pietro Pilo Boyl. "Specificity and Redundancy of Profilin 1 and 2 Function in Brain Development and Neuronal Structure." Cells 10, no. 9 (September 3, 2021): 2310. http://dx.doi.org/10.3390/cells10092310.
Анотація:
Profilin functions have been discussed in numerous cellular processes, including actin polymerization. One puzzling aspect is the concomitant expression of more than one profilin isoform in most tissues. In neuronal precursors and in neurons, profilin 1 and profilin 2 are co-expressed, but their specific and redundant functions in brain morphogenesis are still unclear. Using a conditional knockout mouse model to inactivate both profilins in the developing CNS, we found that threshold levels of profilin are necessary for the maintenance of the neuronal stem-cell compartment and the generation of the differentiated neurons, irrespective of the specific isoform. During embryonic development, profilin 1 is more abundant than profilin 2; consequently, modulation of profilin 1 levels resulted in a more severe phenotype than depletion of profilin 2. Interestingly, the relevance of the isoforms was reversed in the postnatal brain. Morphology of mature neurons showed a stronger dependence on profilin 2, since this is the predominant isoform in neurons. Our data highlight redundant functions of profilins in neuronal precursor expansion and differentiation, as well as in the maintenance of pyramidal neuron dendritic arborization. The specific profilin isoform is less relevant; however, a threshold profilin level is essential. We propose that the common activity of profilin 1 and profilin 2 in actin dynamics is responsible for the observed compensatory effects.
41
Hakim, Zeenat S., Laura A. DiMichele, Jason T. Doherty, Jonathon W. Homeister, Hilary E. Beggs, Louis F. Reichardt, Robert J. Schwartz, et al. "Conditional Deletion of Focal Adhesion Kinase Leads to Defects in Ventricular Septation and Outflow Tract Alignment." Molecular and Cellular Biology 27, no. 15 (May 25, 2007): 5352–64. http://dx.doi.org/10.1128/mcb.00068-07.
Анотація:
ABSTRACT To examine a role for focal adhesion kinase (FAK) in cardiac morphogenesis, we generated a line of mice with a conditional deletion of FAK in nkx2-5-expressing cells (herein termed FAKnk mice). FAKnk mice died shortly after birth, likely resulting from a profound subaortic ventricular septal defect and associated malalignment of the outflow tract. Additional less penetrant phenotypes included persistent truncus arteriosus and thickened valve leaflets. Thus, conditional inactivation of FAK in nkx2-5-expressing cells leads to the most common congenital heart defect that is also a subset of abnormalities associated with tetralogy of Fallot and the DiGeorge syndrome. No significant differences in proliferation or apoptosis between control and FAKnk hearts were observed. However, decreased myocardialization was observed for the conal ridges of the proximal outflow tract in FAKnk hearts. Interestingly, chemotaxis was significantly attenuated in isolated FAK-null cardiomyocytes in comparison to genetic controls, and these effects were concomitant with reduced tyrosine phosphorylation of Crk-associated substrate (CAS). Thus, it is possible that ventricular septation and appropriate outflow tract alignment is dependent, at least in part, upon FAK-dependent CAS activation and subsequent induction of polarized myocyte movement into the conal ridges. Future studies will be necessary to determine the precise contributions of the additional nkx2-5-derived lineages to the phenotypes observed.
42
Deleuze, Virginie, Elias Chalhoub, Rawan El-Hajj, Christiane Dohet, Mikaël Le Clech, Pierre-Olivier Couraud, Philippe Huber, and Danièle Mathieu. "TAL-1/SCL and Its Partners E47 and LMO2 Up-Regulate VE-Cadherin Expression in Endothelial Cells." Molecular and Cellular Biology 27, no. 7 (January 22, 2007): 2687–97. http://dx.doi.org/10.1128/mcb.00493-06.
Анотація:
ABSTRACT The basic helix-loop-helix TAL-1/SCL essential for hematopoietic development is also required during vascular development for embryonic angiogenesis. We reported that TAL-1 acts positively on postnatal angiogenesis by stimulating endothelial morphogenesis. Here, we investigated the functional consequences of TAL-1 silencing in human primary endothelial cells. We found that TAL-1 knockdown caused the inhibition of in vitro tubulomorphogenesis, which was associated with a dramatic reduction in vascular endothelial cadherin (VE-cadherin) at intercellular junctions. Consistently, silencing of TAL-1 as well as of its cofactors E47 and LMO2 down-regulated VE-cadherin at both the mRNA and the protein level. Endogenous VE-cadherin transcription could be activated in nonendothelial HEK-293 cells by the sole concomitant ectopic expression of TAL-1, E47, and LMO2. Transient transfections in human primary endothelial cells derived from umbilical vein (HUVECs) demonstrated that VE-cadherin promoter activity was dependent on the integrity of a specialized E-box associated with a GATA motif and was maximal with the coexpression of the different components of the TAL-1 complex. Finally, chromatin immunoprecipitation assays showed that TAL-1 and its cofactors occupied the VE-cadherin promoter in HUVECs. Together, these data identify VE-cadherin as a bona fide target gene of the TAL-1 complex in the endothelial lineage, providing a first clue to TAL-1 function in angiogenesis.
43
Blais, Jaime D., Christina L. Addison, Robert Edge, Theresa Falls, Huijun Zhao, Kishore Wary, Costas Koumenis, et al. "Perk-Dependent Translational Regulation Promotes Tumor Cell Adaptation and Angiogenesis in Response to Hypoxic Stress." Molecular and Cellular Biology 26, no. 24 (October 9, 2006): 9517–32. http://dx.doi.org/10.1128/mcb.01145-06.
Анотація:
ABSTRACT It has been well established that the tumor microenvironment can promote tumor cell adaptation and survival. However, the mechanisms that influence malignant progression have not been clearly elucidated. We have previously demonstrated that cells cultured under hypoxic/anoxic conditions and transformed cells in hypoxic areas of tumors activate a translational control program known as the integrated stress response (ISR). Here, we show that tumors derived from K-Ras-transformed Perk−/− mouse embryonic fibroblasts (MEFs) are smaller and exhibit less angiogenesis than tumors with an intact ISR. Furthermore, Perk promotes a tumor microenvironment that favors the formation of functional microvessels. These observations were corroborated by a microarray analysis of polysome-bound RNA in aerobic and hypoxic Perk+/+ and Perk−/− MEFs. This analysis revealed that a subset of proangiogenic transcripts is preferentially translated in a Perk-dependent manner; these transcripts include VCIP, an adhesion molecule that promotes cellular adhesion, integrin binding, and capillary morphogenesis. Taken with the concomitant Perk-dependent translational induction of additional proangiogenic genes identified by our microarray analysis, this study suggests that Perk plays a role in tumor cell adaptation to hypoxic stress by regulating the translation of angiogenic factors necessary for the development of functional microvessels and further supports the contention that the Perk pathway could be an attractive target for novel antitumor modalities.
44
Merkel, G. J. "Effects of culture conditions on the in vitro infection of fibroblasts by Candida albicans." Canadian Journal of Microbiology 38, no. 2 (February 1, 1992): 135–42. http://dx.doi.org/10.1139/m92-022.
Анотація:
The effects of yeast culture age, carbon source, growth temperature, and germ-tube inducers on adherence to primary fibroblast cultures was studied in conjunction with the determination of adherence-mediated mammalian cell damage by measuring chromium-51 release from fibroblast monolayers. The results indicated that yeast culture age affected adherence only when the yeasts were grown at 37 °C, not after growth at 28 °C. At 37 °C, quantitatively fewer exponential-phase, glucose- or galactose-grown yeasts adhered to fibroblasts than did yeasts that were in lag or stationary phases. The reduced adherence correlated with less chromium-51 release and reduced germ-tube formation. The addition of germ-tube inducers, such as N-acetyl-D-glucosamine or serum, to exponential-phase yeasts caused an increase in germ-tube formation with a concomitant increase in yeast adherence and release of chromium-51 from the monolayers. Exponential-phase galactose-grown yeasts were more responsive to serum-induced germ-tube formation, germ-tube elongation, and fibroblast adherence than were exponential-phase glucose-grown yeasts. In addition, exponential-phase galactose-grown yeasts caused more chromium-51 release from monolayers in the presence of serum than did glucose-grown yeasts. Overall, conditions that enhanced germ-tube formation and elongation resulted in greatest adherence-mediated damage to the monolayers. Key words: Candida albicans, fibroblasts, morphogenesis.
45
Levantini, Elena, Francesco Cerisoli, Francesca Bertolotti, Valentina Antonelli, Daniele Galvagno, Daniel G. Tenen, Trang Hoang, and Cristina M. Magli. "Role of Otx1 in the Differentiation of Myelo-Monocytic Precursors." Blood 106, no. 11 (November 16, 2005): 388. http://dx.doi.org/10.1182/blood.v106.11.388.388.
Анотація:
Abstract Homeobox-containing genes encode transcription factors implicated in the development and differentiation of multiple cell systems, including hematopoiesis. Several lines of evidence, obtained in our laboratory, indicate that Otx1, a homeobox gene of the paired class strictly required for brain morphogenesis, plays an important role also in blood cell production. It is differentially expressed in hematopoietic progenitors, particularly within the erythroid lineage and loss of Otx1 function results in a cell-autonomous erythroid impairment. Furthermore, Otx1 contributes to the control of erythropoiesis through a direct action on Scl/Tal1, a major hematopoietic regulator. In this study we have investigated whether Otx1 is also implicated in the regulation of myelo-monocytic differentiation. Analysis of Otx1 expression indicated that the gene is transcriptionally active in myelo-monocytic precursors. Moreover, using clonogenic assays we observed that Otx1−/− mice display abnormal frequencies of bone marrow myeloid subpopulations, although the total number of myeloid precursors is normal, as compared to wild type animals. Inactivation of Otx1 leads to a significant decrease of myelo-monocytic (CFU-GM) and monocytic (CFU-M) progenitors, and a concomitant increase of granulocytic precursors (CFU-G). In addition, morphological analysis of Otx1−/− bone marrow cells confirmed a high percentage of cells of the granulocytic lineage. Furthermore, at the molecular level, we detected in null mutant cells the upregulation of the gene encoding the G-CSF receptor and the modulation of other key myeloid regulators. Finally, to understand whether the action of Otx1 in myeloid cells is, like in erythoid cells, mediated by Scl we tested whether expression of a Scl transgene in Otx1−/− mice can re-establish normal ratios between the myeloid subpopulations. Results showed that, in contrast to the findings within the erythroid compartment, constitutive Scl expression does not fully rescue the alterations within the myelo-monocytic lineage. Taken together our data indicate that the brain morphogenetic gene Otx1 is an important regulator of the blood system, as it plays a relevant role in erythropoiesis, and contributes to control also myelo-monocytic differentiation, likely at the level of the commitment events of bipotential progenitor cells.
46
Singh, J., and DJ Handelsman. "Morphometric studies of neonatal estrogen imprinting in the mature mouse prostate." Journal of Endocrinology 162, no. 1 (July 1, 1999): 39–48. http://dx.doi.org/10.1677/joe.0.1620039.
Анотація:
Estrogens play an important role in prostate physiology and neonatal exposure to estrogens has profound effects on the mature structure and hormonal sensitivity of rodent prostate. We aimed to determine the long-term effects of neonatal estrogens on the ductal architecture, morphology and hormonal sensitivity of the mature mouse prostate. Newborn mice (day 1-2) were administered a single injection (s.c.) of estrogens (estradiol benzoate (EB), diethylstilbestrol (DES)) with or without concomitant anti-estrogens (tamoxifen (TAM) or ICI 182 780 (ICI)) TAM or ICI alone, GnRH-antagonist (GnRH-A) or vehicle. At 7 weeks of age, ventral prostates (VP) were microdissected to estimate branch tip numbers and processed for stereologic analysis of volume fractions and diameters of various tissue components. Estrogens induced permanently reduced branching morphogenesis leading to reduced VP weights and these effects were fully reproduced by GnRH-A, consistent with an indirect effect. Stereologically, neonatal estrogens induced epithelial and stromal hyperplasia and significantly reduced (P<0.05) the diameters of VP glandular tubules and lumen compared with controls and these regressive effects were not reversed either by TAM or ICI. These studies confirm that a single neonatal dose of both DES and EB produces imprinting in the mature mouse prostate and indicate that neonatal estrogen effects involve both direct as well as indirect effects. In addition, both TAM and ICI act as partial agonists to the estrogen receptor in the ventral prostate of neonatal mouse.
47
Huang, Lijiang, Yan Peng, Xuetao Tao, Xiaoxiao Ding, Rui Li, Yongsheng Jiang, and Wei Zuo. "Microtubule Organization Is Essential for Maintaining Cellular Morphology and Function." Oxidative Medicine and Cellular Longevity 2022 (March 7, 2022): 1–15. http://dx.doi.org/10.1155/2022/1623181.
Анотація:
Microtubules (MTs) are highly dynamic polymers essential for a wide range of cellular physiologies, such as acting as directional railways for intracellular transport and position, guiding chromosome segregation during cell division, and controlling cell polarity and morphogenesis. Evidence has established that maintaining microtubule (MT) stability in neurons is vital for fundamental cellular and developmental processes, such as neurodevelopment, degeneration, and regeneration. To fulfill these diverse functions, the nervous system employs an arsenal of microtubule-associated proteins (MAPs) to control MT organization and function. Subsequent studies have identified that the disruption of MT function in neurons is one of the most prevalent and important pathological features of traumatic nerve damage and neurodegenerative diseases and that this disruption manifests as a reduction in MT polymerization and concomitant deregulation of the MT cytoskeleton, as well as downregulation of microtubule-associated protein (MAP) expression. A variety of MT-targeting agents that reverse this pathological condition, which is regarded as a therapeutic opportunity to intervene the onset and development of these nervous system abnormalities, is currently under development. Here, we provide an overview of the MT-intrinsic organization process and how MAPs interact with the MT cytoskeleton to promote MT polymerization, stabilization, and bundling. We also highlight recent advances in MT-targeting therapeutic agents applied to various neurological disorders. Together, these findings increase our current understanding of the function and regulation of MT organization in nerve growth and regeneration.
48
Šmahel, Zbyněk, and Božena Škvařilová. "Length of the Cervical Spine as a Factor in the Etiology of Cleft Palate." Cleft Palate-Craniofacial Journal 30, no. 3 (May 1993): 274–78. http://dx.doi.org/10.1597/1545-1569_1993_030_0274_lotcsa_2.3.co_2.
Анотація:
The length of the cervical spine in a series of 206 adult males with cleft lip and/or palate and 50 normal controls was measured. The patients were divided into five subgroups according to the type and extent of the cleft. The shortening of the spine was most marked in bilateral cleft lip and palate patients (complete), less marked in unilateral cleft lip and palate patients, and was slight in isolated cleft palate patients. Complete isolated cleft palate and cleft lip was not associated with a shortening of the spine. A shortening of the cervical spine in less extensive types of isolated cleft palate was suggestive of the participation of the spine in their development, while in cleft lip and palate a simultaneous exposure to a teratogenic agent or any other developmental error during early stages of embryogenesis could explain the concomitant occurrence of spine anomalies. Patients with cleft lip and palate associated with a short spine also had a shorter mandibular ramus, which could be suggestive of simultaneous damage to both structures during morphogenesis. This relationship was not demonstrated in isolated cleft palate that developed in later stages of embryogenesis. In these cases a short spine itself could not have impaired the growth potential of the mandible, yet it could have mechanically induced the development of cleft palate. These observations are in agreement with the present state of knowledge on the development of orofacial clefts as shown in experimental animals.
49
Grimm, Sandra L., Tiffany N. Seagroves, Elena B. Kabotyanski, Russell C. Hovey, Barbara K. Vonderhaar, John P. Lydon, Keiko Miyoshi, et al. "Disruption of Steroid and Prolactin Receptor Patterning in the Mammary Gland Correlates with a Block in Lobuloalveolar Development." Molecular Endocrinology 16, no. 12 (December 1, 2002): 2675–91. http://dx.doi.org/10.1210/me.2002-0239.
Анотація:
Abstract Targeted deletion of the bZIP transcription factor, CCAAT/enhancer binding protein-β (C/EBPβ), was shown previously to result in aberrant ductal morphogenesis and decreased lobuloalveolar development, accompanied by an altered pattern of progesterone receptor (PR) expression. Here, similar changes in the level and pattern of prolactin receptor (PrlR) expression were observed while screening for differentially expressed genes in C/EBPβnull mice. PR patterning was also altered in PrlRnull mice, as well as in mammary tissue transplants from both PrlRnull and signal transducer and activator of transcription (Stat) 5a/b-deficient mice, with concomitant defects in hormone-induced proliferation. Down-regulation of PR and activation of Stat5 phosphorylation were seen after estrogen and progesterone treatment in both C/EBPβnull and wild-type mice, indicating that these signaling pathways were functional, despite the failure of steroid hormones to induce proliferation. IGF binding protein-5, IGF-II, and insulin receptor substrate-1 all displayed altered patterns and levels of expression in C/EBPβnull mice, suggestive of a change in the IGF signaling axis. In addition, small proline-rich protein (SPRR2A), a marker of epidermal differentiation, and keratin 6 were misexpressed in the mammary epithelium of C/EBPβnull mice. Together, these data suggest that C/EBPβ is a master regulator of mammary epithelial cell fate and that the correct spatial pattern of PR and PrlR expression is a critical determinant of hormone-regulated cell proliferation.
50
Ito, Shota, Tomoko Minamizaki, Shohei Kohno, Yusuke Sotomaru, Yoshiaki Kitaura, Shinsuke Ohba, Toshie Sugiyama, Jane E. Aubin, Kotaro Tanimoto, and Yuji Yoshiko. "Overexpression of miR-125b in Osteoblasts Improves Age-Related Changes in Bone Mass and Quality through Suppression of Osteoclast Formation." International Journal of Molecular Sciences 22, no. 13 (June 23, 2021): 6745. http://dx.doi.org/10.3390/ijms22136745.
Анотація:
We recently reported an unexpected role of osteoblast-derived matrix vesicles in the delivery of microRNAs to bone matrix. Of such microRNAs, we found that miR-125b inhibited osteoclast formation by targeting Prdm1 encoding a transcriptional repressor of anti-osteoclastogenesis factors. Transgenic (Tg) mice overexpressing miR-125b in osteoblasts by using human osteocalcin promoter grow normally but exhibit high trabecular bone mass. We have now further investigated the effects of osteoblast-mediated miR-125b overexpression on skeletal morphogenesis and remodeling during development, aging and in a situation of skeletal repair, i.e., fracture healing. There were no significant differences in the growth plate, primary spongiosa or lateral (periosteal) bone formation and mineral apposition rate between Tg and wild-type (WT) mice during early bone development. However, osteoclast number and medial (endosteal) bone resorption were less in Tg compared to WT mice, concomitant with increased trabecular bone mass. Tg mice were less susceptible to age-dependent changes in bone mass, phosphate/amide I ratio and mechanical strength. In a femoral fracture model, callus formation progressed similarly in Tg and WT mice, but callus resorption was delayed, reflecting the decreased osteoclast numbers associated with the Tg callus. These results indicate that the decreased osteoclastogenesis mediated by miR-125b overexpression in osteoblasts leads to increased bone mass and strength, while preserving bone formation and quality. They also suggest that, in spite of the fact that single miRNAs may target multiple genes, the miR-125b axis may be an attractive therapeutic target for bone loss in various age groups.