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1
Nance, Jeremy, und James R. Priess. „Cell polarity and gastrulation inC. elegans“. Development 129, Nr. 2 (15.01.2002): 387–97. http://dx.doi.org/10.1242/dev.129.2.387.
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Gastrulation in C. elegans embryos involves formation of a blastocoel and the ingression of surface cells into the blastocoel. Mutations in the par-3 gene cause abnormal separations between embryonic cells, suggesting that the PAR-3 protein has a role in blastocoel formation. In normal development, PAR proteins localize to either the apical or basal surfaces of cells prior to blastocoel formation; we demonstrate that this localization is determined by cell contacts. Cells that ingress into the blastocoel undergo an apical flattening associated with an apical concentration of non-muscle myosin. We provide evidence that ingression times are determined by genes that control cell fate, though interactions with neighboring cells can prevent ingression.
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Olson, Sara K., Joseph R. Bishop, John R. Yates, Karen Oegema und Jeffrey D. Esko. „Identification of novel chondroitin proteoglycans in Caenorhabditis elegans: embryonic cell division depends on CPG-1 and CPG-2“. Journal of Cell Biology 173, Nr. 6 (19.06.2006): 985–94. http://dx.doi.org/10.1083/jcb.200603003.
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Vertebrates produce multiple chondroitin sulfate proteoglycans that play important roles in development and tissue mechanics. In the nematode Caenorhabditis elegans, the chondroitin chains lack sulfate but nevertheless play essential roles in embryonic development and vulval morphogenesis. However, assignment of these functions to specific proteoglycans has been limited by the lack of identified core proteins. We used a combination of biochemical purification, Western blotting, and mass spectrometry to identify nine C. elegans chondroitin proteoglycan core proteins, none of which have homologues in vertebrates or other invertebrates such as Drosophila melanogaster or Hydra vulgaris. CPG-1/CEJ-1 and CPG-2 are expressed during embryonic development and bind chitin, suggesting a structural role in the egg. RNA interference (RNAi) depletion of individual CPGs had no effect on embryonic viability, but simultaneous depletion of CPG-1/CEJ-1 and CPG-2 resulted in multinucleated single-cell embryos. This embryonic lethality phenocopies RNAi depletion of the SQV-5 chondroitin synthase, suggesting that chondroitin chains on these two proteoglycans are required for cytokinesis.
3
Schroeder, D. F., und J. D. McGhee. „Anterior-posterior patterning within the Caenorhabditis elegans endoderm“. Development 125, Nr. 24 (15.12.1998): 4877–87. http://dx.doi.org/10.1242/dev.125.24.4877.
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The endoderm of higher organisms is extensively patterned along the anterior/posterior axis. Although the endoderm (gut or E lineage) of the nematode Caenorhabditis elegans appears to be a simple uniform tube, cells in the anterior gut show several molecular and anatomical differences from cells in the posterior gut. In particular, the gut esterase ges-1 gene, which is normally expressed in all cells of the endoderm, is expressed only in the anterior-most gut cells when certain sequences in the ges-1 promoter are deleted. Using such a deleted ges-1 transgene as a biochemical marker of differentiation, we have investigated the basis of anterior-posterior gut patterning in C. elegans. Although homeotic genes are involved in endoderm patterning in other organisms, we show that anterior gut markers are expressed normally in C. elegans embryos lacking genes of the homeotic cluster. Although signalling from the mesoderm is involved in endoderm patterning in other organisms, we show that ablation of all non-gut blastomeres from the C. elegans embryo does not affect anterior gut marker expression; furthermore, ectopic guts produced by genetic transformation express anterior gut markers generally in the expected location and in the expected number of cells. We conclude that anterior gut fate requires no specific cell-cell contact but rather is produced autonomously within the E lineage. Cytochalasin D blocking experiments fully support this conclusion. Finally, the HMG protein POP-1, a downstream component of the Wnt signalling pathway, has recently been shown to be important in many anterior/posterior fate decisions during C. elegans embryogenesis (Lin, R., Hill, R. J. and Priess, J. R. (1998) Cell 92, 229–239). When RNA-mediated interference is used to eliminate pop-1 function from the embryo, gut is still produced but anterior gut marker expression is abolished. We suggest that the C. elegans endoderm is patterned by elements of the Wnt/pop-1 signalling pathway acting autonomously within the E lineage.
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Van Auken, Kimberly, Daniel Weaver, Barbara Robertson, Meera Sundaram, Tassa Saldi, Lois Edgar, Ulrich Elling, Monica Lee, Queta Boese und William B. Wood. „Roles of the Homothorax/Meis/Prep homolog UNC-62 and the Exd/Pbx homologs CEH-20 and CEH-40 in C. elegans embryogenesis“. Development 129, Nr. 22 (15.11.2002): 5255–68. http://dx.doi.org/10.1242/dev.129.22.5255.
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Co-factor homeodomain proteins such as Drosophila Homothorax (Hth)and Extradenticle (Exd) and their respective vertebrate homologs, the Meis/Prep and Pbx proteins, can increase the DNA-binding specificity of Hox protein transcription factors and appear to be required for many of their developmental functions. We show that the unc-62 gene encodes theC. elegans ortholog of Hth, and that maternal-effect unc-62mutations can cause severe posterior disorganization during embryogenesis (Nob phenotype), superficially similar to that seen in embryos lacking function of either the two posterior-group Hox genes nob-1 and php-3 or the caudal homolog pal-1. Other zygotically actingunc-62 alleles cause earlier embryonic arrest or incompletely penetrant larval lethality with variable morphogenetic defects among the survivors, suggesting that unc-62 functions are required at several stages of development. The differential accumulation of four unc-62transcripts is consistent with multiple functions. The C. elegans exdhomologs ceh-20 and ceh-40 interact genetically withunc-62 and may have overlapping roles in embryogenesis: neither CEH-20 nor CEH-40 appears to be required when the other is present, but loss of both functions causes incompletely penetrant embryonic lethality in the presence of unc-62(+) and complete embryonic lethality in the presence of an unc-62 hypomorphic allele.
5
Schierenberg, Einhard. „Early development of nematode embryos: differences and similarities“. Nematology 2, Nr. 1 (2000): 57–64. http://dx.doi.org/10.1163/156854100508890.
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AbstractTo determine whether embryogenesis of Caenorhabditis elegans is typical for nematodes in general, we started to analyse in comparison several aspects of development in various nematode species. The differences we observed can be subdivided into two classes, those visible in the intact embryo and those requiring experimental interference. Particularly obvious differences of both types were revealed between C. elegans (Rhabditidae) and Acrobeloides nanus (Cephalobidae). Not only does the spatial and temporal pattern of early events differ but also that of intercellular communication and cell specification. Our data suggest that some developmental variations are characteristic for certain nematode groups and therefore may be useful as phylogenetic markers. In contrast, we detected little evidence so far for environmental influence on early developmental processes. Pour déterminer dans quelle mesure l’embryogenèse de Caenorhabditis elegans est une caractéristique générale des nématodes, nous avons commencé l’analyse de plusieurs aspects du développement chez différentes espèces de nématodes. Les différences observées peuvent être divisées en deux catégories: celles observables chez l’embryon intact et celles nécessitant une intervention expérimentale. En particulier, des différences nettes entre les deux catégories ont été mises en évidence chez C. elegans (Rhabditidae) et Acrobeloides nanus (Cephalobidae). Diffèrent non seulement le schéma spatio-temporel des évènements précoces, mais également la communication intercellulaire et la différenciation cellulaire. Nos données suggèrent que certaines variations du développement sont caractéristiques de certains groupes de nématodes et pourraient donc être utiles comme marqueurs phylogénétiques. A contrario, une influence de l’environnement sur les processus précoces du développement n’a pas, jusqu’à présent, été détectée.
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Coomans, August, Myriam Claeys, Gaëtan Borgonie und Christopher Link. „Lysosomal and pseudocoelom routing protects Caenorhabditis elegans from ricin toxicity“. Nematology 5, Nr. 3 (2003): 339–50. http://dx.doi.org/10.1163/156854103769224331.
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AbstractThe resistance of the nematode Caenorhabditis elegans towards the highly potent toxin ricin has been studied. Incubation of C. elegans in ricin did not affect life span or progeny production. However, micro-injection of the ricin A-chain into the distal, syncitial gonad caused degeneration and sterility in test specimens, confirming that C. elegans ribosomes are sensitive. Using transmission electron microscopy, it was observed that ricin is effectively internalised into the intestinal cells. When pre-labelled with gold, the toxin reached only the lysosomes. When native toxin was used, the toxin was either routed to the lysosomes or underwent transcytosis to the pseudocoelomatic cavity and incorporation into embryos. None of the ricin reached either the trans Golgi network or the Golgi apparatus, considered essential for toxicity. The observed oral non-toxicity is therefore due to alternate sorting of the toxin, a mechanism not previously observed. The data indicate that, although ricin can opportunistically bind to, and be internalised by, cell surface receptors, these receptors are not sufficient to elicit toxicity.
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Ferreira, Helder C., Benjamin D. Towbin, Thibaud Jegou und Susan M. Gasser. „The shelterin protein POT-1 anchors Caenorhabditis elegans telomeres through SUN-1 at the nuclear periphery“. Journal of Cell Biology 203, Nr. 5 (02.12.2013): 727–35. http://dx.doi.org/10.1083/jcb.201307181.
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Telomeres are specialized protein–DNA structures that protect chromosome ends. In budding yeast, telomeres form clusters at the nuclear periphery. By imaging telomeres in embryos of the metazoan Caenorhabditis elegans, we found that telomeres clustered only in strains that had activated an alternative telomere maintenance pathway (ALT). Moreover, as in yeast, the unclustered telomeres in wild-type embryos were located near the nuclear envelope (NE). This bias for perinuclear localization increased during embryogenesis and persisted in differentiated cells. Telomere position in early embryos required the NE protein SUN-1, the single-strand binding protein POT-1, and the small ubiquitin-like modifier (SUMO) ligase GEI-17. However, in postmitotic larval cells, none of these factors individually were required for telomere anchoring, which suggests that additional mechanisms anchor in late development. Importantly, targeted POT-1 was sufficient to anchor chromatin to the NE in a SUN-1–dependent manner, arguing that its effect at telomeres is direct. This high-resolution description of telomere position within C. elegans extends our understanding of telomere organization in eukaryotes.
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Labouesse, M., E. Hartwieg und H. R. Horvitz. „The Caenorhabditis elegans LIN-26 protein is required to specify and/or maintain all non-neuronal ectodermal cell fates“. Development 122, Nr. 9 (01.09.1996): 2579–88. http://dx.doi.org/10.1242/dev.122.9.2579.
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The C. elegans gene lin-26, which encodes a presumptive zinc-finger transcription factor, is required for hypodermal cells to acquire their proper fates. Here we show that lin-26 is expressed not only in all hypodermal cells but also in all glial-like cells. During asymmetric cell divisions that generate a neuronal cell and a non-neuronal cell, LIN-26 protein is symmetrically segregated and then lost from the neuronal cell. Expression in glial-like cells (socket and sheath cells) is biologically important, as some of these neuronal support cells die or seem sometimes to be transformed to neuron-like cells in embryos homozygous for strong loss-of-function mutations. In addition, most of these glial-like cells are structurally and functionally defective in animals carrying the weak loss-of-function mutation lin-26(n156). lin-26 mutant phenotypes and expression patterns together suggest that lin-26 is required to specify and/or maintain the fates not only of hypodermal cells but also of all other non-neuronal ectodermal cells in C. elegans. We speculate that lin-26 acts by repressing the expression of neuronal-specific genes in non-neuronal cells.
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Osório, Daniel S., Fung-Yi Chan, Joana Saramago, Joana Leite, Ana M. Silva, Ana F. Sobral, Reto Gassmann und Ana Xavier Carvalho. „Crosslinking activity of non-muscle myosin II is not sufficient for embryonic cytokinesis in C. elegans“. Development 146, Nr. 21 (03.10.2019): dev179150. http://dx.doi.org/10.1242/dev.179150.
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10
Kowalski, M. P., H. A. Baylis und T. Krude. „Non-coding stem-bulge RNAs are required for cell proliferation and embryonic development in C. elegans“. Journal of Cell Science 128, Nr. 11 (23.04.2015): 2118–29. http://dx.doi.org/10.1242/jcs.166744.
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11
Kowalski, M. P., H. A. Baylis und T. Krude. „Non-coding stem-bulge RNAs are required for cell proliferation and embryonic development in C. elegans“. Development 142, Nr. 12 (15.06.2015): e1204-e1204. http://dx.doi.org/10.1242/dev.126771.
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12
Harfe, B. D., C. S. Branda, M. Krause, M. J. Stern und A. Fire. „MyoD and the specification of muscle and non-muscle fates during postembryonic development of the C. elegans mesoderm“. Development 125, Nr. 13 (01.07.1998): 2479–88. http://dx.doi.org/10.1242/dev.125.13.2479.
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Basic-helix-loop helix factors of the myoD/myf5/ myogenin/MRF4 family have been implicated in acquisition and elaboration of muscle cell fates. Here we describe both myogenic and non-myogenic roles for the Caenorhabditis elegans member of this family (CeMyoD) in postembryonic mesodermal patterning. The postembryonic mesodermal lineage in C. elegans provides a paradigm for many of the issues in mesodermal fate specification: a single mesoblast ('M') divides to generate 14 striated muscles, 16 non-striated muscles, and two non-muscle cells. To study CeMyoD function in the M lineage, we needed to circumvent an embryonic requirement for the protein. Two approaches were used: (1) isolation of mutants that decrease CeMyoD levels while retaining viability, and (2) analysis of genetic mosaics that had lost CeMyoD in the M lineage. With either manipulation, we observed a series of cell-fate transformations affecting a subset of both striated muscles and non-muscle cells. In place of these normal fates, the affected lineages produced a number of myoblast-like cells that initially failed to differentiate, instead swelling to acquire a resemblance to sex myoblasts (M-lineage-derived precursors to non-striated uterine and vulval muscles). Like normal sex myoblasts, the ectopic myoblast-like cells were capable of migration and proliferation followed by differentiation of progeny cells into vulval and uterine muscle. Our results demonstrate a cell-intrinsic contribution of CeMyoD to specification of both non-muscle and muscle fates.
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Corsi, A. K., S. A. Kostas, A. Fire und M. Krause. „Caenorhabditis elegans twist plays an essential role in non-striated muscle development“. Development 127, Nr. 10 (15.05.2000): 2041–51. http://dx.doi.org/10.1242/dev.127.10.2041.
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The basic helix-loop-helix (bHLH) transcription factor Twist plays a role in mesodermal development in both invertebrates and vertebrates. In an effort to understand the role of the unique Caenorhabditis elegans Twist homolog, hlh-8, we analyzed mesodermal development in animals with a deletion in the hlh-8 locus. This deletion was predicted to represent a null allele because the HLH domain is missing and the reading frame for the protein is disrupted. Animals lacking CeTwist function were constipated and egg-laying defective. Both of these defects were rescued in transgenic mutant animals expressing wild-type hlh-8. Observing a series of mesoderm-specific markers allowed us to characterize the loss of hlh-8 function more thoroughly. Our results demonstrate that CeTwist performs an essential role in the proper development of a subset of mesodermal tissues in C. elegans. We found that CeTwist was required for the formation of three out of the four non-striated enteric muscles born in the embryo. In contrast, CeTwist was not required for the formation of the embryonically derived striated muscles. Most of the post-embryonic mesoderm develops from a single lineage. CeTwist was necessary for appropriate patterning in this lineage and was required for expression of two downstream target genes, but was not required for the expression of myosin, a marker of differentiation. Our results suggest that mesodermal patterning by Twist is an evolutionarily conserved function.
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Turner, Ashley N., Jessica M. Hoffman, Mickie L. Powell, Melissa J. Sammy, Douglas R. Moellering, Tim R. Nagy, Steven N. Austad und Daniel L. Smith. „ASSESSMENT OF A MICROPLATE SYSTEM FOR MEASURING INDIVIDUAL REAL-TIME RESPIRATION IN SMALL MODEL ORGANISMS OF AGING“. Innovation in Aging 3, Supplement_1 (November 2019): S918—S919. http://dx.doi.org/10.1093/geroni/igz038.3347.
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Abstract The ability to measure oxygen consumption rates of a living organism in real-time provides an indirect method of monitoring dynamic changes in metabolism reflecting organismal level mitochondrial function. In this study, we assessed the Loligo Systems microplate system for measuring individual respiration in small organisms. This included adult nematodes (Caenorhabditis elegans, N2), zebrafish embryos (Danio rerio, AB), and adult fruit flies (Drosophila melanogaster, w1118). Organisms were placed inside 80 µL glass chambers on a 24-well microplate atop a 24-channel optical fluorescence oxygen reading device. Adult nematodes and zebrafish embryos were in liquid culture, M9 buffer and egg water respectively, and the adult flies were in room air. The microplate and reader were placed inside an incubator for temperature control. A silicone gasket with a thin liner was used to seal the chambers. Reference standard oxygen consumption (respiration) of single and multiple adult nematodes (n=1–4 animals/well), zebrafish embryos (n=1–4 animals/well), and adult flies (n=1–2 animals/well) in the microplate system were achieved. Significant differences across numbers of animals/well and by sex were observed. Validation experiments of the oxygen consumption rates measured in C. elegans in parallel with Seahorse extracellular flux (XF) experiments are underway. The Loligo Systems microplate system offers a non-invasive, non-destructive method to measure real-time respiration in smaller organisms. These data provide preliminary evidence for utility of the system for a variety of biomedical applications that relate to organismal and mitochondrial function/dysfunction, including research in the basic biology of aging in these highly-utilized, pre-clinical, genetic model organisms.
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Ghazarian, Haike, Catherine Coyle-Thompson, William Dalrymple, Virginia Hutchins-Carroll, Stan Metzenberg, Ziba Razinia, Edward J. Carroll und Steven B. Oppenheimer. „Exogenous hyalin and sea urchin gastrulation. Part IV: a direct adhesion assay – progress in identifying hyalin's active sites“. Zygote 18, Nr. 1 (08.06.2009): 17–26. http://dx.doi.org/10.1017/s0967199409005498.
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SummaryIn Strongylocentrotus purpuratus the hyalins are a set of three to four rather large glycoproteins (hereafter referred to as ‘hyalin’), which are the major constituents of the hyaline layer, the developing sea urchin embryo's extracellular matrix. Recent research from our laboratories has shown that hyalin is a cell adhesion molecule involved in sea urchin embryo-specific cellular interactions. Other laboratories have shown it to consist of 2–3% carbohydrate and a cloned, sequenced fragment demonstrated repeat domains (HYR) and non-repeat regions. Interest in this molecule has increased because HYR has been identified in organisms as diverse as bacteria, flies, worms, mice and humans, as well as sea urchins. Our laboratories have shown that hyalin appears to mediate a specific cellular interaction that has interested investigators for over a century, archenteron elongation/attachment to the blastocoel roof. We have shown this finding by localizing hyalin on the two components of the cellular interaction and by showing that hyalin and anti-hyalin antibody block the cellular interaction using a quantitative microplate assay. The microplate assay, however, has limitations because it does not directly assess hyalin's effects on the adhesion of the two components of the interaction. Here we have used an elegant direct assay that avoids the limitations, in which we microdissected the two components of the adhesive interaction and tested their re-adhesion to each other, thereby avoiding possible factors in the whole embryos that could confound or confuse results. Using both assays, we found that mild periodate treatment (6 h to 24 h in sodium acetate buffer with 0.2 M sodium periodate at 4 °C in the dark) of hyalin eliminates its ability to block the cellular interaction, suggesting that the carbohydrate component(s) may be involved in hyalin's specific adhesive function. This first step is important in identifying the molecular mechanisms of a well known cellular interaction in the NIH-designated sea urchin embryo model, a system that has led to the discovery of scores of physiological mechanisms, including those involved in human health and disease.
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Storfer-Glazer, F. A., und W. B. Wood. „Effects of chromosomal deficiencies on early cleavage patterning and terminal phenotype in Caenorhabditis elegans embryos.“ Genetics 137, Nr. 2 (01.06.1994): 499–508. http://dx.doi.org/10.1093/genetics/137.2.499.
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Abstract We have analyzed pregastrulation cleavage patterns in Caenorhabditis elegans embryos homozygous for various chromosomal deficiencies. By two different estimates these deficiencies represent between 37 and 49% of the genome, including the entire X chromosome and substantial portions of each of the five autosomes. Among these genomic regions, we find none whose absence causes defects in pregastrulation cleavage patterns. We can conclude that there are at most very few genes whose transcription after fertilization is required for normal early patterning of cell divisions. We also scored terminal phenotypes of the homozygous deficiency embryos for stage of arrest and for expression of three tissue-specific differentiation markers. Based on these phenotypes, we have identified regions of the genome that are required for completion of cell proliferation, expression of gut differentiation and entry into morphogenesis. Somewhat surprisingly, embryos in which cell proliferation is arrested at less than 20% of the normal cell number can nevertheless initiate morphogenesis and undergo elongation to the twofold stage. Our results are consistent with the view that many early events in C. elegans embryogenesis are controlled exclusively by maternally produced gene products. However, they are also consistent with the likely possibility that, at least in some deficiency embryos, although cleavage patterns may be normal, blastomere identities are not. In this respect the early cleavages may differ from later lineages, in which cell division patterns appear to be characteristic of cell identity.
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Piekny, Alisa J., und Paul E. Mains. „Rho-binding kinase (LET-502) and myosin phosphatase (MEL-11) regulate cytokinesis in the earlyCaenorhabditis elegansembryo“. Journal of Cell Science 115, Nr. 11 (01.06.2002): 2271–82. http://dx.doi.org/10.1242/jcs.115.11.2271.
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Rho-binding kinase and myosin phosphatase regulate the contraction of actomyosin filaments in non-muscle and smooth muscle cells. Previously, we described the role of C. elegans genes encoding Rho-binding kinase(let-502) and myosin phosphatase targeting subunit (mel-11)in epidermal cell-shape changes that drive morphogenesis and in spermathecal contraction. Here we analyze their roles in a third contractile event,cytokinesis within early embryos. We demonstrate that these genes function together to regulate the rate of cleavage furrow contraction, with Rho-binding kinase/LET-502 mediating contraction, whereas myosin phosphatase/MEL-11 acts as a brake to contraction: early embryonic cleavage often fails or is slowed when let-502 is mutated, whereas mel-11 mutations result in ectopic furrowing and faster furrow ingression. These phenotypes correspond to changes in the levels of phosphorylated regulatory non-muscle myosin light chain (rMLC). The gene products of let-502 and mel-11colocalize at cleavage furrows, and their mutations alleviate one another's defects. rMLC is phosphorylated in let-502; mel-11 double mutants,indicating that a kinase is able to phosphorylate rMLC in the absence of both LET-502 and MEL-11. Genetic and molecular epistasis experiments place LET-502 and MEL-11 in a cytokinetic pathway. LET-502 and MEL-11 regulate the activity of non-muscle myosin after actin, non-muscle myosin heavy chain/NMY-2,regulatory non-muscle myosin light chain/MLC-4 and early formin/CYK-1 have formed a contractile ring. Proteins including Rho GTPase activating protein/CYK-4 and late CYK-1, which are required for late stages of cytokinesis, function downstream of LET-502 and MEL-11.
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Middelkoop, Teije C., Júlia Garcia-Baucells, Porfirio Quintero-Cadena, Lokesh G. Pimpale, Shahrzad Yazdi, Paul W. Sternberg, Peter Gross und Stephan W. Grill. „CYK-1/Formin activation in cortical RhoA signaling centers promotes organismal left–right symmetry breaking“. Proceedings of the National Academy of Sciences 118, Nr. 20 (10.05.2021): e2021814118. http://dx.doi.org/10.1073/pnas.2021814118.
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Proper left–right symmetry breaking is essential for animal development, and in many cases, this process is actomyosin-dependent. In Caenorhabditis elegans embryos active torque generation in the actomyosin layer promotes left–right symmetry breaking by driving chiral counterrotating cortical flows. While both Formins and Myosins have been implicated in left–right symmetry breaking and both can rotate actin filaments in vitro, it remains unclear whether active torques in the actomyosin cortex are generated by Formins, Myosins, or both. We combined the strength of C. elegans genetics with quantitative imaging and thin film, chiral active fluid theory to show that, while Non-Muscle Myosin II activity drives cortical actomyosin flows, it is permissive for chiral counterrotation and dispensable for chiral symmetry breaking of cortical flows. Instead, we find that CYK-1/Formin activation in RhoA foci is instructive for chiral counterrotation and promotes in-plane, active torque generation in the actomyosin cortex. Notably, we observe that artificially generated large active RhoA patches undergo rotations with consistent handedness in a CYK-1/Formin–dependent manner. Altogether, we conclude that CYK-1/Formin–dependent active torque generation facilitates chiral symmetry breaking of actomyosin flows and drives organismal left–right symmetry breaking in the nematode worm.
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Okkema, P. G., und A. Fire. „The Caenorhabditis elegans NK-2 class homeoprotein CEH-22 is involved in combinatorial activation of gene expression in pharyngeal muscle“. Development 120, Nr. 8 (01.08.1994): 2175–86. http://dx.doi.org/10.1242/dev.120.8.2175.
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The pharyngeal muscles of Caenorhabditis elegans are single sarcomere muscles used for feeding. Like vertebrate cardiac and smooth muscles, C. elegans pharyngeal muscle does not express any of the known members of the MyoD family of myogenic factors. To identify mechanisms regulating gene expression in this tissue, we have characterized a pharyngeal muscle-specific enhancer from myo-2, a myosin heavy chain gene expressed exclusively in pharyngeal muscle. Assaying enhancer function in transgenic animals, we identified three subelements, designated A, B and C, that contribute to myo-2 enhancer activity. These subelements are individually inactive; however, any combination of two or more subelements forms a functional enhancer. The B and C subelements have distinct cell type specificities. A duplication of B activates transcription in a subset of pharyngeal muscles (m3, m4, m5 and m7). A duplication of C activates transcription in all pharyngeal cells, muscle and non-muscle. Thus, the activity of the myo-2 enhancer is regulated by a combination of pharyngeal muscle-type-specific and organ-specific signals. Screening a cDNA expression library, we identified a gene encoding an NK-2 class homeodomain protein, CEH-22, that specifically binds a site necessary for activity of the B subelement. CEH-22 protein is first expressed prior to myogenic differentiation and is present in the same subset of pharyngeal muscles in which B is active. Expression continues throughout embryonic and larval development. This expression pattern suggests CEH-22 plays a key role in pharyngeal muscle-specific activity of the myo-2 enhancer.
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Das, P., L. L. Maduzia, H. Wang, A. L. Finelli, S. H. Cho, M. M. Smith und R. W. Padgett. „The Drosophila gene Medea demonstrates the requirement for different classes of Smads in dpp signaling“. Development 125, Nr. 8 (15.04.1998): 1519–28. http://dx.doi.org/10.1242/dev.125.8.1519.
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Signals from transforming growth factor-beta (TGF-beta) ligands are transmitted within the cell by members of the Smad family, which can be grouped into three classes based on sequence similarities. Our previous identification of both class I and II Smads functioning in a single pathway in C. elegans, raised the issue of whether the requirement for Smads derived from different classes is a general feature of TGF-beta signaling. We report here the identification of a new Drosophila class II Smad, Medea, a close homolog of the human tumor-suppressor gene DPC4. Embryos from germline clones of both Medea and Mad (a class I Smad) are ventralized, as are embryos null for the TGF-beta-like ligand decapentaplegic (dpp). Loss of Medea also blocks dpp signaling during later development, suggesting that Medea, like Mad, is universally required for dpp signaling. Furthermore, we show that the necessity for these two closely related, non-redundant Smads, is due to their different signaling properties - upon activation of the Dpp pathway, Mad is required to actively translocate Medea into the nucleus. These results provide a paradigm for, and distinguish between, the requirement for class I and II Smads in Dpp/BMP signaling.
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Saudenova, Makhabbat, und Chantal Wicky. „The Chromatin Remodeler LET-418/Mi2 is Required Cell Non-Autonomously for the Post-Embryonic Development of Caenorhabditis elegans“. Journal of Developmental Biology 7, Nr. 1 (24.12.2018): 1. http://dx.doi.org/10.3390/jdb7010001.
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Chromatin condition is crucial for the cells to respond to their environment. In C. elegans, post-embryonic development is accompanied by the exit of progenitor cells from quiescence in response to food. The chromatin protein LET-418/Mi2 is required for this transition in development indicating that proper chromatin structure in cells of the freshly hatched larvae is important to respond to food. However, the identity of the tissue or cells where LET-418/Mi2 is required, as well as the developmental signals that it is modulating have not been elucidated. By restoring the activity of LET-418/Mi2 in specific tissues, we demonstrate that its activity in the intestine and the hypodermis is able to promote in a cell non-autonomous manner the exit of blast cells from quiescence and further development. Furthermore, we identify the IIS (insulin/insulin-like growth factor signaling) pathway to be one of the signaling pathways that is conveying LET-418/Mi2 cell non-autonomous effect on development.
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Ng, S. C., L. A. Perkins, G. Conboy, N. Perrimon und M. C. Fishman. „A Drosophila gene expressed in the embryonic CNS shares one conserved domain with the mammalian GAP-43“. Development 105, Nr. 3 (01.03.1989): 629–38. http://dx.doi.org/10.1242/dev.105.3.629.
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By cross hybridization with the mammalian growth-related protein, GAP-43, we have isolated several Drosophila cDNAs and genomic sequences. These sequences correspond to a single copy gene that encodes two developmentally regulated transcripts 2.4 and 2.0 kb in length. The predicted protein sequence from the cDNAs contains a stretch of 20 amino acids closely related to the mammalian GAP-43 protein. These residues are also highly conserved in a cDNA isolated from the nematode C. elegans. Prior to dorsal closure, expression of the Drosophila gene is observed in non-neuronal tissues, especially in the mesectoderm and presumptive epidermis, both in a metameric pattern. After dorsal closure, expression becomes restricted to sets of cells that are segmentally reiterated along the periphery of the nervous system. These cells appear to include at least one specific set of glia that may establish scaffolding for the development of the longitudinal neuropile.
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Zambrano, Nicola, Marida Bimonte, Salvatore Arbucci, Davide Gianni, Tommaso Russo und Paolo Bazzicalupo. „feh-1 and apl-1, the Caenorhabditis elegansorthologues of mammalian Fe65 and β-amyloid precursor protein genes, are involved in the same pathway that controls nematode pharyngeal pumping“. Journal of Cell Science 115, Nr. 7 (01.04.2002): 1411–22. http://dx.doi.org/10.1242/jcs.115.7.1411.
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The multigenic family of mammalian Fe65s encodes three highly similar proteins with the same modular organisation: a WW domain and two phosphotyrosine-binding domains. The PTB2 domain of these proteins binds to the cytosolic domains of the Alzheimer's β-amyloid precursor protein APP and related proteins APLP1 and APLP2, generating a highly redundant system that is hard to dissect by reverse genetics. By searching potential Fe65-like genes in the nematode Caenorhabditis elegans, we identified a single gene, feh-1 (Fe65 homolog-1), encoding a protein with a high sequence similarity to mammalian Fe65s. FEH-1 is also functionally related to mammalian orthologues;in fact its PTB2 domain binds to APL-1, the product of the C. elegansorthologue of APP. Staining with specific antibodies show that the neuromuscular structures of the pharynx are the sites in which FEH-1 is present at highest levels. Expression studies with reporters indicate that the feh-1 gene is also expressed by a subset of the worm neurons. We generated and isolated a deletion allele of feh-1, and the corresponding homozygous mutants arrest as late embryos or as L1 larvae,demonstrating for the first time an essential role for a Fe65-like gene in vivo. The pharynx of homozygous larvae does not contract and the worms cannot feed. Analysis of pharyngeal pumping in heterozygous worms and in feh-1 RNA-interfered worms indicates that dosage of feh-1function affects the rate of pharyngeal contraction in C. elegans. Interference with apl-1 double-stranded RNA showed a similar effect on pharyngeal pumping, suggesting that FEH-1 and APL-1 are involved in the same pathway. The non-redundant system of the nematode will prove useful for studying the basic biology of the Fe65-APP interaction and the molecular events regulated by this evolutionarily conserved system of interacting proteins.
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Koh, Kyunghee, und Joel H. Rothman. „ELT-5 and ELT-6 are required continuously to regulate epidermal seam cell differentiation and cell fusion inC. elegans“. Development 128, Nr. 15 (01.08.2001): 2867–80. http://dx.doi.org/10.1242/dev.128.15.2867.
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The C. elegans epidermis is a simple epithelium comprised of three major cell types, the seam, syncytial and P cells. While specification of all major epidermal cells is known to require the ELT-1 GATA transcription factor, little is known about how the individual epidermal cell types are specified. We report that elt-5 and -6, adjacent genes encoding GATA factors, are essential for the development of the lateral epidermal cells, the seam cells. Inhibition of elt-5 and -6 function by RNA-mediated interference results in penetrant late embryonic and early larval lethality. Seam cells in affected animals do not differentiate properly: the alae, seam-specific cuticular structures, are generally absent and expression of several seam-specific markers is blocked. In addition, elt-3, which encodes another GATA factor normally expressed in non-seam epidermis, is often ectopically expressed in the seam cells of affected animals, demonstrating that ELT-5 and -6 repress elt-3 expression in wild-type seam cells. Seam cells in affected animals often undergo inappropriate fusion with the epidermal syncytia. Interference of elt-5 and -6 function during larval development can cause fusion of all seam cells with the surrounding syncytia and pronounced defects in molting. elt-5 and -6 are both expressed in seam cells and many other cells, and are apparently functionally interchangeable. Their expression is controlled by separable tissue-specific regulatory elements and the apportionment of monocistronic versus dicistronic transcription of both genes appears to be subject to cell-type-specific regulation. Collectively, these findings indicate that elt-5 and -6 function continuously throughout C. elegans development to regulate seam cell differentiation and cell fusion.
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Ferguson, Kimberly C., und Joel H. Rothman. „Alterations in the Conserved SL1trans-Spliced Leader of Caenorhabditis elegansDemonstrate Flexibility in Length and Sequence Requirements In Vivo“. Molecular and Cellular Biology 19, Nr. 3 (01.03.1999): 1892–900. http://dx.doi.org/10.1128/mcb.19.3.1892.
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ABSTRACT Approximately 70% of mRNAs in Caenorhabditis elegansare trans spliced to conserved 21- to 23-nucleotide leader RNAs. While the function of SL1, the major C. elegans trans-spliced leader, is unknown, SL1 RNA, which contains this leader, is essential for embryogenesis. Efforts to characterize in vivo requirements of the SL1 leader sequence have been severely constrained by the essential role of the corresponding DNA sequences in SL1 RNA transcription. We devised a heterologous expression system that circumvents this problem, making it possible to probe the length and sequence requirements of the SL1 leader without interfering with its transcription. We report that expression of SL1 from a U2 snRNA promoter rescues mutants lacking the SL1-encoding genes and that the essential embryonic function of SL1 is retained when approximately one-third of the leader sequence and/or the length of the leader is significantly altered. In contrast, although all mutant SL1 RNAs were well expressed, more severe alterations eliminate this essential embryonic function. The one non-rescuing mutant leader tested was never detected on messages, demonstrating that part of the leader sequence is essential for trans splicing in vivo. Thus, in spite of the high degree of SL1 sequence conservation, its length, primary sequence, and composition are not critical parameters of its essential embryonic function. However, particular nucleotides in the leader are essential for the in vivo function of the SL1 RNA, perhaps for its assembly into a functional snRNP or for the trans-splicing reaction.
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Akay, Alper, Ashley Craig, Nicolas Lehrbach, Mark Larance, Ehsan Pourkarimi, Jane E. Wright, Angus Lamond, Eric Miska und Anton Gartner. „RNA-binding protein GLD-1/quaking genetically interacts with the mir-35 and the let- 7 miRNA pathways in Caenorhabditis elegans“. Open Biology 3, Nr. 11 (November 2013): 130151. http://dx.doi.org/10.1098/rsob.130151.
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Messenger RNA translation is regulated by RNA-binding proteins and small non-coding RNAs called microRNAs. Even though we know the majority of RNA-binding proteins and microRNAs that regulate messenger RNA expression, evidence of interactions between the two remain elusive. The role of the RNA-binding protein GLD-1 as a translational repressor is well studied during Caenorhabditis elegans germline development and maintenance. Possible functions of GLD-1 during somatic development and the mechanism of how GLD-1 acts as a translational repressor are not known. Its human homologue, quaking (QKI), is essential for embryonic development. Here, we report that the RNA-binding protein GLD-1 in C. elegans affects multiple microRNA pathways and interacts with proteins required for microRNA function. Using genome-wide RNAi screening, we found that nhl-2 and vig-1 , two known modulators of miRNA function, genetically interact with GLD-1. gld-1 mutations enhance multiple phenotypes conferred by mir-35 and let-7 family mutants during somatic development. We used stable isotope labelling with amino acids in cell culture to globally analyse the changes in the proteome conferred by let-7 and gld-1 during animal development. We identified the histone mRNA-binding protein CDL-1 to be, in part, responsible for the phenotypes observed in let-7 and gld-1 mutants. The link between GLD-1 and miRNA-mediated gene regulation is further supported by its biochemical interaction with ALG-1, CGH-1 and PAB-1, proteins implicated in miRNA regulation. Overall, we have uncovered genetic and biochemical interactions between GLD-1 and miRNA pathways.
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Murray, John Isaac, Elicia Preston, Jeremy P. Crawford, Jonathan D. Rumley, Prativa Amom, Breana D. Anderson, Priya Sivaramakrishnan et al. „The anterior Hox gene ceh-13 and elt-1/GATA activate the posterior Hox genes nob-1 and php-3 to specify posterior lineages in the C. elegans embryo“. PLOS Genetics 18, Nr. 5 (02.05.2022): e1010187. http://dx.doi.org/10.1371/journal.pgen.1010187.
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Hox transcription factors play a conserved role in specifying positional identity during animal development, with posterior Hox genes typically repressing the expression of more anterior Hox genes. Here, we dissect the regulation of the posterior Hox genes nob-1 and php-3 in the nematode C. elegans. We show that nob-1 and php-3 are co-expressed in gastrulation-stage embryos in cells that previously expressed the anterior Hox gene ceh-13. This expression is controlled by several partially redundant transcriptional enhancers. These enhancers act in a ceh-13-dependant manner, providing a striking example of an anterior Hox gene positively regulating a posterior Hox gene. Several other regulators also act positively through nob-1/php-3 enhancers, including elt-1/GATA, ceh-20/ceh-40/Pbx, unc-62/Meis, pop-1/TCF, ceh-36/Otx, and unc-30/Pitx. We identified defects in both cell position and cell division patterns in ceh-13 and nob-1;php-3 mutants, suggesting that these factors regulate lineage identity in addition to positional identity. Together, our results highlight the complexity and flexibility of Hox gene regulation and function and the ability of developmental transcription factors to regulate different targets in different stages of development.
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Villeneuve, A. M., und B. J. Meyer. „The role of sdc-1 in the sex determination and dosage compensation decisions in Caenorhabditis elegans.“ Genetics 124, Nr. 1 (01.01.1990): 91–114. http://dx.doi.org/10.1093/genetics/124.1.91.
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Abstract Our previous work demonstrated that mutations in the X-linked gene sdc-1 disrupt both sex determination and dosage compensation in Caenorhabditis elegans XX animals, suggesting that sdc-1 acts at a step that is shared by the sex determination and dosage compensation pathways prior to their divergence. In this report, we extend our understanding of early events in C. elegans sex determination and dosage compensation and the role played by sdc-1 in these processes. First, our analysis of 14 new sdc-1 alleles suggests that the phenotypes resulting from the lack of sdc-1 function are (1) an incompletely penetrant sexual transformation of XX animals toward the male fate, and (2) increased levels of X-linked gene transcripts in XX animals, correlated with XX-specific morphological defects but not significant XX-specific lethality. Further, all alleles exhibit strong maternal rescue for all phenotypes assayed. Second, temperature-shift experiments suggest that sdc-1 acts during the first half of embryogenesis in determining somatic sexual phenotype, long before sexual differentiation actually takes place, and consistent with our previous proposal that sdc-1 acts at an early step in the regulatory hierarchy controlling the choice of sexual fate. Other temperature-shift experiments suggest that sdc-1 may be involved in establishing but not maintaining the XX mode of dosage compensation. Third, a genetic mosaic analysis of sdc-1 produced an unusual result: the genotypic mosaics failed to display the sdc-1 sexual transformation phenotypes. This result suggests several possible interpretations: (1) sdc-1 is expressed immediately, in the one- or two-celled embryo; (2) sdc-1 acts non-cell-autonomously, such that expression of the gene in either the AB or P1 lineage can supply sdc-1(+) function to cells of the other lineage; (3) the X/A ratio is assessed immediately, in the one- or two-celled embryo; or (4) the X/A signal directs the choice of sexual fate in a non-cell-autonomous fashion. Finally, examination of the classes of sexual phenotypes produced in sdc-1 mutant strains suggests that different cells in the organism may not choose their sexual fates independently.
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Ferretti, Luca, Andrea Krämer-Eis und Philipp H. Schiffer. „Conserved Patterns in Developmental Processes and Phases, Rather than Genes, Unite the Highly Divergent Bilateria“. Life 10, Nr. 9 (06.09.2020): 182. http://dx.doi.org/10.3390/life10090182.
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Bilateria are the predominant clade of animals on Earth. Despite having evolved a wide variety of body plans and developmental modes, they are characterized by common morphological traits. By default, researchers have tried to link clade-specific genes to these traits, thus distinguishing bilaterians from non-bilaterians, by their gene content. Here we argue that it is rather biological processes that unite Bilateria and set them apart from their non-bilaterian sisters, with a less complex body morphology. To test this hypothesis, we compared proteomes of bilaterian and non-bilaterian species in an elaborate computational pipeline, aiming to search for a set of bilaterian-specific genes. Despite the limited confidence in their bilaterian specificity, we nevertheless detected Bilateria-specific functional and developmental patterns in the sub-set of genes conserved in distantly related Bilateria. Using a novel multi-species GO-enrichment method, we determined the functional repertoire of genes that are widely conserved among Bilateria. Analyzing expression profiles in three very distantly related model species—D. melanogaster, D. rerio and C. elegans—we find characteristic peaks at comparable stages of development and a delayed onset of expression in embryos. In particular, the expression of the conserved genes appears to peak at the phylotypic stage of different bilaterian phyla. In summary, our study illustrate how development connects distantly related Bilateria after millions of years of divergence, pointing to processes potentially separating them from non-bilaterians. We argue that evolutionary biologists should return from a purely gene-centric view of evolution and place more focus on analyzing and defining conserved developmental processes and periods.
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Giblin-Davis, Robin M., Natsumi Kanzaki, Paul De Ley, Donna S. Williams, Einhard Schierenberg, Erik J. Ragsdale, Yongsan Zeng und Barbara J. Center. „Ultrastructure and life history of Myolaimus byersi n. sp. (Myolaimina: Myolaimidae), a phoretic associate of the crane fly, Limonia schwarzi (Alexander) (Limoniidae), in Florida“. Nematology 12, Nr. 4 (2010): 519–42. http://dx.doi.org/10.1163/138855409x12519673803912.
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Abstract Myolaimus byersi n. sp., a phoretic associate of the crane fly, Limonia (Rhipidia) schwarzi (Diptera: Limoniidae), was recovered from moist and decaying tissue from the crown shaft of a living spindle palm, Hyophorbe verschaffeltii, in southern Florida and is described herein. Dauers were carried in the abdominal folds of male and female L. schwarzi. Examination of the highly mobile crane fly larvae and pupae confirmed that the dauers were externally associated with the cuticle. Dauers from crane flies were culturable to adults on 1/20 strength TSB agar. The association appears to be relatively host specific. SEM studies, early embryonic development, dauers, molecular data and TEM ultrastructural comparisons of the stoma, sensory structures and sperm are used to discuss the relative placement of Myolaimus within the Nematoda. The stoma resembles diplogastrids in being strongly anisomorphic with an enlarged dorsal sector of the stegostom, yet also resembles rhabditids in having three triangular flaps in the metastegostom and matches cephalobs and panagrolaims in having a pharyngeal collar with two sets of three interradial muscles followed by two sets of six adradial muscles. The ultrastructure of the cheilostom epidermis shows a high degree of conservation with several Rhabditida. The sperm of M. byersi n. sp. is nearly identical to that of Caenorhabditis elegans. In early cell division, M. byersi n. sp. is closest to Parascaris equorum followed by C. elegans. Myolaimus apparently represents a divergent lineage that has followed a non-coalescing trajectory for a long time, allowing it to retain some highly conserved characters while also developing some surprisingly unique features, such as a baggy cuticle and males that lack a gubernaculum or spicules.
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Bennett, D. C., P. J. Cooper, T. J. Dexter, L. M. Devlin, J. Heasman und B. Nester. „Cloned mouse melanocyte lines carrying the germline mutations albino and brown: complementation in culture“. Development 105, Nr. 2 (01.02.1989): 379–85. http://dx.doi.org/10.1242/dev.105.2.379.
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We have established two new immortal lines of mouse melanocytes, melan-b and melan-c, from mice homozygous for the brown (b) and albino (c) mutations respectively. Both lines were derived through differentiation in vitro of embryonic epidermal melanoblasts. The brown melanocytes are visibly brown by light microscopy, and centrifuged cell suspensions form brown pellets. The albino melanocytes form white pellets and contain abundant unpigmented premelanosomes as shown by transmission electron microscopy. Like normal, non-immortal melanocytes and like the immortal black melanocyte line melan-a, both lines show little or no growth in a standard, serum-supplemented medium, but proliferate well in the presence of 12-o-tetradecanoyl phorbol-13-acetate (TPA). Sustained growth of the albino cells also requires either keratinocyte feeder cells or 2-mercaptoethanol (2-ME). The modal chromosome numbers are 39 for melan-b and 40 (diploid) for melan-c. Neither line is tumorigenic in nude mice. Heterokaryons between the two lines can be constructed and form wild-type, black pigment. Melanocyte lines can now be reproducibly generated from mice of different strains, and provide tools for molecular studies of germline coat-colour mutations. These two lines provide elegant means to study the developmentally controlled expression of the two complementary genes, B and C, with black melanin pigment as a readily detectable natural marker.
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Herman, M. „C. elegans POP-1/TCF functions in a canonical Wnt pathway that controls cell migration and in a noncanonical Wnt pathway that controls cell polarity“. Development 128, Nr. 4 (15.02.2001): 581–90. http://dx.doi.org/10.1242/dev.128.4.581.
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In Caenorhabditis elegans, Wnt signaling pathways are important in controlling cell polarity and cell migrations. In the embryo, a novel Wnt pathway functions through a (beta)-catenin homolog, WRM-1, to downregulate the levels of POP-1/Tcf in the posterior daughter of the EMS blastomere. The level of POP-1 is also lower in the posterior daughters of many anteroposterior asymmetric cell divisions during development. I have found that this is the case for of a pair of postembryonic blast cells in the tail. In wild-type animals, the level of POP-1 is lower in the posterior daughters of the two T cells, TL and TR. Furthermore, in lin-44/Wnt mutants, in which the polarities of the T cell divisions are frequently reversed, the level of POP-1 is frequently lower in the anterior daughters of the T cells. I have used a novel RNA-mediated interference technique to interfere specifically with pop-1 zygotic function and have determined that pop-1 is required for wild-type T cell polarity. Surprisingly, none of the three C. elegans (beta)-catenin homologs appeared to function with POP-1 to control T cell polarity. Wnt signaling by EGL-20/Wnt controls the migration of the descendants of the QL neuroblast by regulating the expression the Hox gene mab-5. Interfering with pop-1 zygotic function caused defects in the migration of the QL descendants that mimicked the defects in egl-20/Wnt mutants and blocked the expression of mab-5. This suggests that POP-1 functions in the canonical Wnt pathway to control QL descendant migration and in novel Wnt pathways to control EMS and T cell polarities.
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WILLIAMS, Richard T., Shehnaaz S. M. MANJI, Nigel J. PARKER, Manuela S. HANCOCK, Leonie van STEKELENBURG, Jean-Pierre EID, Paul V. SENIOR et al. „Identification and characterization of the STIM (stromal interaction molecule) gene family: coding for a novel class of transmembrane proteins“. Biochemical Journal 357, Nr. 3 (25.07.2001): 673–85. http://dx.doi.org/10.1042/bj3570673.
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STIM1 (where STIM is stromal interaction molecule) is a candidate tumour suppressor gene that maps to human chromosome 11p15.5, a region implicated in a variety of cancers, particularly embryonal rhabdomyosarcoma. STIM1 codes for a transmembrane phosphoprotein whose structure is unrelated to that of any other known proteins. The precise pathway by which STIM1 regulates cell growth is not known. In the present study we screened gene databases for STIM1-related sequences, and have identified and characterized cDNA sequences representing a single gene in humans and other vertebrates, which we have called STIM2. We identified a single STIM homologue in Drosophila melanogaster (D-Stim) and Caenorhabditis elegans, but no homologues in yeast. STIM1, STIM2 and D-Stim have a conserved genomic organization, indicating that the vertebrate family of two STIM genes most probably arose from a single ancestral gene. The three STIM proteins each contain a single SAM (sterile α-motif) domain and an unpaired EF hand within the highly conserved extracellular region, and have coiled-coil domains that are conserved in structure and position within the cytoplasmic region. However, the STIM proteins diverge significantly within the C-terminal half of the cytoplasmic domain. Differential levels of phosphorylation appear to account for two molecular mass isoforms (105 and 115kDa) of STIM2. We demonstrate by mutation analysis and protein sequencing that human STIM2 initiates translation exclusively from a non-AUG start site in vivo. STIM2 is expressed ubiquitously in cell lines, and co-precipitates with STIM1 from cell lysates. This association into oligomers in vivo indicates a possible functional interaction between STIM1 and STIM2. The structural similarities between STIM1, STIM2 and D-STIM suggest conserved biological functions.
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Koh, Kyunghee, Sara M. Peyrot, Cricket G. Wood, Javier A. Wagmaister, Morris F. Maduro, David M. Eisenmann und Joel H. Rothman. „Cell fates and fusion in theC. elegansvulval primordium are regulated by the EGL-18 and ELT-6 GATA factors — apparent direct targets of the LIN-39 Hox protein“. Development 129, Nr. 22 (15.11.2002): 5171–80. http://dx.doi.org/10.1242/dev.129.22.5171.
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Development of the vulva in C. elegans is mediated by the combinatorial action of several convergent regulatory inputs, three of which,the Ras, Wnt and Rb-related pathways, act by regulating expression of thelin-39 Hox gene. LIN-39 specifies cell fates and regulates cell fusion in the mid-body region, leading to formation of the vulva. In the lateral seam epidermis, differentiation and cell fusion have been shown to be regulated by two GATA-type transcription factors, ELT-5 and -6. We report that ELT-5 is encoded by the egl-18 gene, which was previously shown to promote formation of a functional vulva. Furthermore, we find that EGL-18(ELT-5), and its paralogue ELT-6, are redundantly required to regulate cell fates and fusion in the vulval primordium and are essential to form a vulva. Elimination of egl-18 and elt-6 activity results in arrest by the first larval stage; however, in animals rescued for this larval lethality by expression of ELT-6 in non-vulval cells, the post-embryonic cells(P3.p-P8.p) that normally become vulval precursor cells often fuse with the surrounding epidermal syncytium or undergo fewer than normal cell divisions,reminiscent of lin-39 mutants. Moreover, egl-18/elt-6reporter gene expression in the developing vulva is attenuated inlin-39(rf) mutants, and overexpression of egl-18 can partially rescue the vulval defects caused by reduced lin-39activity. LIN-39/CEH-20 heterodimers bind two consensus HOX/PBC sites in a vulval enhancer region of egl-18/elt-6, one of which is essential for vulval expression of egl-18/elt-6 reporter constructs. These findings demonstrate that the EGL-18 and ELT-6 GATA factors are essential, genetically redundant regulators of cell fates and fusion in the developing vulva and are apparent direct transcriptional targets of the LIN-39 Hox protein.
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Ansaloni, Federico, Margherita Scarpato, Elia Di Schiavi, Stefano Gustincich und Remo Sanges. „Exploratory analysis of transposable elements expression in the C. elegans early embryo“. BMC Bioinformatics 20, S9 (November 2019). http://dx.doi.org/10.1186/s12859-019-3088-7.
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Abstract Background Transposable Elements (TE) are mobile sequences that make up large portions of eukaryote genomes. The functions they play within the complex cellular architecture are still not clearly understood, but it is becoming evident that TE have a role in several physiological and pathological processes. In particular, it has been shown that TE transcription is necessary for the correct development of mice embryos and that their expression is able to finely modulate transcription of coding and non-coding genes. Moreover, their activity in the central nervous system (CNS) and other tissues has been correlated with the creation of somatic mosaicisms and with pathologies such as neurodevelopmental and neurodegenerative diseases as well as cancers. Results We analyzed TE expression among different cell types of the Caenorhabditis elegans (C. elegans) early embryo asking if, where and when TE are expressed and whether their expression is correlated with genes playing a role in early embryo development. To answer these questions, we took advantage of a public C. elegans embryonic single-cell RNA-seq (sc-RNAseq) dataset and developed a bioinformatics pipeline able to quantify reads mapping specifically against TE, avoiding counting reads mapping on TE fragments embedded in coding/non-coding transcripts. Our results suggest that i) canonical TE expression analysis tools, which do not discard reads mapping on TE fragments embedded in annotated transcripts, may over-estimate TE expression levels, ii) Long Terminal Repeats (LTR) elements are mostly expressed in undifferentiated cells and might play a role in pluripotency maintenance and activation of the innate immune response, iii) non-LTR are expressed in differentiated cells, in particular in neurons and nervous system-associated tissues, and iv) DNA TE are homogenously expressed throughout the C. elegans early embryo development. Conclusions TE expression appears finely modulated in the C. elegans early embryo and different TE classes are expressed in different cell types and stages, suggesting that TE might play diverse functions during early embryo development.
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Sun, Yan, Qichao Yu, Lei Li, Zhanlong Mei, Biaofeng Zhou, Shang Liu, Taotao Pan et al. „Single-cell RNA profiling links ncRNAs to spatiotemporal gene expression during C. elegans embryogenesis“. Scientific Reports 10, Nr. 1 (02.11.2020). http://dx.doi.org/10.1038/s41598-020-75801-3.
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Abstract Recent studies show that non-coding RNAs (ncRNAs) can regulate the expression of protein-coding genes and play important roles in mammalian development. Previous studies have revealed that during C. elegans (Caenorhabditis elegans) embryo development, numerous genes in each cell are spatiotemporally regulated, causing the cell to differentiate into distinct cell types and tissues. We ask whether ncRNAs participate in the spatiotemporal regulation of genes in different types of cells and tissues during the embryogenesis of C. elegans. Here, by using marker-free full-length high-depth single-cell RNA sequencing (scRNA-seq) technique, we sequence the whole transcriptomes from 1031 embryonic cells of C. elegans and detect 20,431 protein-coding genes, including 22 cell-type-specific protein-coding markers, and 9843 ncRNAs including 11 cell-type-specific ncRNA markers. We induce a ncRNAs-based clustering strategy as a complementary strategy to the protein-coding gene-based clustering strategy for single-cell classification. We identify 94 ncRNAs that have never been reported to regulate gene expressions, are co-expressed with 1208 protein-coding genes in cell type specific and/or embryo time specific manners. Our findings suggest that these ncRNAs could potentially influence the spatiotemporal expression of the corresponding genes during the embryogenesis of C. elegans.
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Yu, Hsiang, Huey-Jen Lai, Tai-Wei Lin und Szecheng J. Lo. „Autonomous and non-autonomous roles of DNase II during cell death in C. elegans embryos“. Bioscience Reports 35, Nr. 3 (01.06.2015). http://dx.doi.org/10.1042/bsr20150055.
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The method of ToLFP (topoisomerase labelled fluorescence probes) is useful for detecting the DNA fragments generated by DNase II in Caenorhabditis elegans embryos. It reveals ~70% ToLFP signals in dying cells and 30% in engulfing cells during embryogenesis.
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Thijssen, Karen L., Melanie van der Woude, Carlota Davó-Martínez, Dick H. W. Dekkers, Mariangela Sabatella, Jeroen A. A. Demmers, Wim Vermeulen und Hannes Lans. „C. elegans TFIIH subunit GTF-2H5/TTDA is a non-essential transcription factor indispensable for DNA repair“. Communications Biology 4, Nr. 1 (25.11.2021). http://dx.doi.org/10.1038/s42003-021-02875-8.
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AbstractThe 10-subunit TFIIH complex is vital to transcription and nucleotide excision repair. Hereditary mutations in its smallest subunit, TTDA/GTF2H5, cause a photosensitive form of the rare developmental disorder trichothiodystrophy. Some trichothiodystrophy features are thought to be caused by subtle transcription or gene expression defects. TTDA/GTF2H5 knockout mice are not viable, making it difficult to investigate TTDA/GTF2H5 in vivo function. Here we show that deficiency of C. elegans TTDA ortholog GTF-2H5 is, however, compatible with life, in contrast to depletion of other TFIIH subunits. GTF-2H5 promotes TFIIH stability in multiple tissues and is indispensable for nucleotide excision repair, in which it facilitates recruitment of TFIIH to DNA damage. Strikingly, when transcription is challenged, gtf-2H5 embryos die due to the intrinsic TFIIH fragility in absence of GTF-2H5. These results support the idea that TTDA/GTF2H5 mutations cause transcription impairment underlying trichothiodystrophy and establish C. elegans as model for studying pathogenesis of this disease.
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Wibisono, Phillip, Yiyong Liu und Jingru Sun. „A novel in vitro Caenorhabditis elegans transcription system“. BMC Molecular and Cell Biology 21, Nr. 1 (30.11.2020). http://dx.doi.org/10.1186/s12860-020-00332-8.
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Abstract Background Caenorhabditis elegans is an excellent model organism for biological research, but its contributions to biochemical elucidation of eukaryotic transcription mechanisms have been limited. One of the biggest obstacles for C. elegans biochemical studies is the high difficulty of obtaining functionally active nuclear extract due to its thick surrounding cuticle. A C. elegans in vitro transcription system was once developed by Lichtsteiner and Tjian in the 1990s, but it has not become widely used, most likely because the transcription reactions were re-constituted with nuclear extract from embryos, not from larval or adult worms, and the method of Dounce homogenization used to prepare the nuclear extract could lead to protein instability. Besides Dounce homogenization, several other techniques were developed to break worms, but no transcription reactions were re-constituted following worm disruption using these approaches. A C. elegans transcription system with effective preparation of functionally active nuclear extract from larval or adult worms has yet to be established. Additionally, non-radioactive methods for detecting transcription as alternatives to the conventional radioactive detection also need to be adapted into such an in vitro system. Results By employing Balch homogenization, we achieved effective disruption of larval and adult worms and obtained functionally active nuclear extract through subcellular fractionation. In vitro transcription reactions were successfully re-constituted using such nuclear extract. Furthermore, a PCR-based non-radioactive detection method was adapted into our system to either qualitatively or quantitatively detect transcription. Using this system to assess how pathogen infection affects C. elegans transcription revealed that Pseudomonas aeruginosa infection changes transcription activity in a promoter- or gene-specific manner. Conclusions In this study, we developed an in vitro C. elegans transcription system that re-constitutes transcription reactions with nuclear extract of larval or adult worms and can both qualitatively and quantitatively detect transcription activity using non-radioactive approaches. This in vitro system is useful for biochemically studying C. elegans transcription mechanisms and gene expression regulation. The effective preparation of functionally active nuclear extract in our system fills a technical gap in biochemical studies of C. elegans and will expand the usefulness of this model organism in addressing many biological questions beyond transcription.
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Haruta, Nami, Eisuke Sumiyoshi, Yu Honda, Masahiro Terasawa, Chihiro Uchiyama, Mika Toya, Yukihiko Kubota und Asako Sugimoto. „Germline-specific role for unconventional components of the γ-tubulin complex in Caenorhabditis elegans“. Journal of Cell Science, 14.06.2023. http://dx.doi.org/10.1242/jcs.260922.
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The γ-tubulin complex (γTuC) is a widely conserved microtubule nucleator, but some of its components GCP4–6 have not been detected in Caenorhabditis elegans. Here, we identified two γTuC-associated proteins in C. elegans, namely GTAP-1 and -2, for which apparent orthologs were detected only in the genus Caenorhabditis. They were localized at centrosomes and the plasma membrane of the germline, and their centrosomal localization was interdependent. In early C. elegans embryos, whereas the conserved γTuC component MZT-1/MOZART1 was essential for the localization of centrosomal γ-tubulin, depletion of GTAP-1 and/or -2 caused up to 50% reduction of centrosomal γ-tubulin and precocious disassembly of spindle poles during mitotic telophase. In the adult germline, GTAP-1 and GTP-2 contributed to the efficient recruitment of γTuC to the plasma membrane. Depletion of GTAP-1, but not GTAP-2, severely disrupted both the microtubule array and the honeycomb-like structure in the adult germline. We propose that GTAP-1 and -2 are unconventional components of γTuC that contribute to the organization of both centrosomal and non-centrosomal microtubules by targeting the γTuC to specific subcellular sites in a tissue-specific manner.
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Quarato, Piergiuseppe, Meetali Singh, Eric Cornes, Blaise Li, Loan Bourdon, Florian Mueller, Celine Didier und Germano Cecere. „Germline inherited small RNAs facilitate the clearance of untranslated maternal mRNAs in C. elegans embryos“. Nature Communications 12, Nr. 1 (04.03.2021). http://dx.doi.org/10.1038/s41467-021-21691-6.
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AbstractInheritance and clearance of maternal mRNAs are two of the most critical events required for animal early embryonic development. However, the mechanisms regulating this process are still largely unknown. Here, we show that together with maternal mRNAs,C. elegansembryos inherit a complementary pool of small non-coding RNAs that facilitate the cleavage and removal of hundreds of maternal mRNAs. These antisense small RNAs are loaded into the maternal catalytically-active Argonaute CSR-1 and cleave complementary mRNAs no longer engaged in translation in somatic blastomeres. Induced depletion of CSR-1 specifically during embryonic development leads to embryonic lethality in a slicer-dependent manner and impairs the degradation of CSR-1 embryonic mRNA targets. Given the conservation of Argonaute catalytic activity, we propose that a similar mechanism operates to clear maternal mRNAs during the maternal-to-zygotic transition across species.
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Wang, Jennifer T., Jarrett Smith, Bi-Chang Chen, Helen Schmidt, Dominique Rasoloson, Alexandre Paix, Bramwell G. Lambrus, Deepika Calidas, Eric Betzig und Geraldine Seydoux. „Regulation of RNA granule dynamics by phosphorylation of serine-rich, intrinsically disordered proteins in C. elegans“. eLife 3 (23.12.2014). http://dx.doi.org/10.7554/elife.04591.
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RNA granules have been likened to liquid droplets whose dynamics depend on the controlled dissolution and condensation of internal components. The molecules and reactions that drive these dynamics in vivo are not well understood. In this study, we present evidence that a group of intrinsically disordered, serine-rich proteins regulate the dynamics of P granules in C. elegans embryos. The MEG (maternal-effect germline defective) proteins are germ plasm components that are required redundantly for fertility. We demonstrate that MEG-1 and MEG-3 are substrates of the kinase MBK-2/DYRK and the phosphatase PP2APPTR−½. Phosphorylation of the MEGs promotes granule disassembly and dephosphorylation promotes granule assembly. Using lattice light sheet microscopy on live embryos, we show that GFP-tagged MEG-3 localizes to a dynamic domain that surrounds and penetrates each granule. We conclude that, despite their liquid-like behavior, P granules are non-homogeneous structures whose assembly in embryos is regulated by phosphorylation.
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Barnes, Kristopher M., Li Fan, Mark W. Moyle, Christopher A. Brittin, Yichi Xu, Daniel A. Colón-Ramos, Anthony Santella und Zhirong Bao. „Cadherin preserves cohesion across involuting tissues during C. elegans neurulation“. eLife 9 (08.10.2020). http://dx.doi.org/10.7554/elife.58626.
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The internalization of the central nervous system, termed neurulation in vertebrates, is a critical step in embryogenesis. Open questions remain regarding how force propels coordinated tissue movement during the process, and little is known as to how internalization happens in invertebrates. We show that in C. elegans morphogenesis, apical constriction in the retracting pharynx drives involution of the adjacent neuroectoderm. HMR-1/cadherin mediates this process via inter-tissue attachment, as well as cohesion within the neuroectoderm. Our results demonstrate that HMR-1 is capable of mediating embryo-wide reorganization driven by a centrally located force generator, and indicate a non-canonical use of cadherin on the basal side of an epithelium that may apply to vertebrate neurulation. Additionally, we highlight shared morphology and gene expression in tissues driving involution, which suggests that neuroectoderm involution in C. elegans is potentially homologous with vertebrate neurulation and thus may help elucidate the evolutionary origin of the brain.
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Zhang, Pu, Taylor N. Medwig-Kinney und Bob Goldstein. „Architecture of the cortical actomyosin network driving apical constriction in C. elegans“. Journal of Cell Biology 222, Nr. 9 (23.06.2023). http://dx.doi.org/10.1083/jcb.202302102.
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Apical constriction is a cell shape change that drives key morphogenetic events during development, including gastrulation and neural tube formation. The forces driving apical constriction are primarily generated through the contraction of apicolateral and/or medioapical actomyosin networks. In the Drosophila ventral furrow, the medioapical actomyosin network has a sarcomere-like architecture, with radially polarized actin filaments and centrally enriched non-muscle myosin II and myosin activating kinase. To determine if this is a broadly conserved actin architecture driving apical constriction, we examined actomyosin architecture during C. elegans gastrulation, in which two endodermal precursor cells internalize from the surface of the embryo. Quantification of protein localization showed that neither the non-muscle myosin II NMY-2 nor the myosin-activating kinase MRCK-1 is enriched at the center of the apex. Further, visualization of barbed- and pointed-end capping proteins revealed that actin filaments do not exhibit radial polarization at the apex. Our results demonstrate that C. elegans endodermal precursor cells apically constrict using a mixed-polarity actin filament network and with myosin and a myosin activator distributed throughout the network. Taken together with observations made in other organisms, our results demonstrate that diverse actomyosin architectures are used in animal cells to accomplish apical constriction.
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Velez-Aguilera, Griselda, Sylvia Nkombo Nkoula, Batool Ossareh-Nazari, Jana Link, Dimitra Paouneskou, Lucie Van Hove, Nicolas Joly et al. „PLK-1 promotes the merger of the parental genome into a single nucleus by triggering lamina disassembly“. eLife 9 (08.10.2020). http://dx.doi.org/10.7554/elife.59510.
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Life of sexually reproducing organisms starts with the fusion of the haploid egg and sperm gametes to form the genome of a new diploid organism. Using the newly fertilized Caenorhabditis elegans zygote, we show that the mitotic Polo-like kinase PLK-1 phosphorylates the lamin LMN-1 to promote timely lamina disassembly and subsequent merging of the parental genomes into a single nucleus after mitosis. Expression of non-phosphorylatable versions of LMN-1, which affect lamina depolymerization during mitosis, is sufficient to prevent the mixing of the parental chromosomes into a single nucleus in daughter cells. Finally, we recapitulate lamina depolymerization by PLK-1 in vitro demonstrating that LMN-1 is a direct PLK-1 target. Our findings indicate that the timely removal of lamin is essential for the merging of parental chromosomes at the beginning of life in C. elegans and possibly also in humans, where a defect in this process might be fatal for embryo development.
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Castiglioni, Victoria G., Helena R. Pires, Rodrigo Rosas Bertolini, Amalia Riga, Jana Kerver und Mike Boxem. „Epidermal PAR-6 and PKC-3 are essential for larval development of C. elegans and organize non-centrosomal microtubules“. eLife 9 (10.12.2020). http://dx.doi.org/10.7554/elife.62067.
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The cortical polarity regulators PAR-6, PKC-3, and PAR-3 are essential for the polarization of a broad variety of cell types in multicellular animals. In C. elegans, the roles of the PAR proteins in embryonic development have been extensively studied, yet little is known about their functions during larval development. Using inducible protein degradation, we show that PAR-6 and PKC-3, but not PAR-3, are essential for postembryonic development. PAR-6 and PKC-3 are required in the epidermal epithelium for animal growth, molting, and the proper pattern of seam-cell divisions. Finally, we uncovered a novel role for PAR-6 in organizing non-centrosomal microtubule arrays in the epidermis. PAR-6 was required for the localization of the microtubule organizer NOCA-1/Ninein, and defects in a noca-1 mutant are highly similar to those caused by epidermal PAR-6 depletion. As NOCA-1 physically interacts with PAR-6, we propose that PAR-6 promotes non-centrosomal microtubule organization through localization of NOCA-1/Ninein.
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Shabtai, Reut, und Yonatan B. Tzur. „Male-specific roles of lincRNA in C. elegans fertility“. Frontiers in Cell and Developmental Biology 11 (23.03.2023). http://dx.doi.org/10.3389/fcell.2023.1115605.
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The testis is the mammalian tissue with the highest expression levels of long intergenic non-coding RNAs (lincRNAs). However, most in vivo models have not found significant reductions in male fertility when highly expressed lincRNA genes were removed. This suggests that certain lincRNAs may act redundantly or lack functional roles. In the genome of the nematode Caenorhabditis elegans, there is an order of magnitude fewer lincRNA genes than in mammals. This characteristic lowers the potential for redundancy, making it an ideal model to test these possibilities. We identified five highly and dynamically expressed lincRNAs in male C. elegans gonads and quantified the fertility of worm strains in which these genes were removed. In contrast to the hermaphrodites of deletion strains, which exhibited no significant reductions in broods, smaller brood sizes were observed in the progeny of males of three of the lincRNA deleted strains. This demonstrates reduced male fertility in worms with those genes removed. Interestingly, reduced brood size was statistically significant only in the last days of egg laying in two of these strains. This suggests the effect is due to early deterioration and aging of the transferred sperm. We detected a mild increase in embryonic lethality in only one of the strains, supporting the possibility that these lincRNAs do not affect fertility through critical roles in essential meiotic processes. Together our results indicate a sexually dimorphic outcome on fertility when lincRNA are removed and show that, unlike mammals, individual lincRNAs in C. elegans do play significant roles in male fertility.
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Moukhtari, Souhaila H. El, Amanda Muñoz-Juan, Rubén Del Campo-Montoya, Anna Laromaine und María J. Blanco-Prieto. „Biosafety evaluation of etoposide lipid nanomedicines in C. elegans“. Drug Delivery and Translational Research, 16.02.2024. http://dx.doi.org/10.1007/s13346-023-01466-w.
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AbstractNeuroblastoma is a pediatric tumor that originates during embryonic development and progresses into aggressive tumors, primarily affecting children under two years old. Many patients are diagnosed as high-risk and undergo chemotherapy, often leading to short- and long-term toxicities. Nanomedicine offers a promising solution to enhance drug efficacy and improve physical properties. In this study, lipid-based nanomedicines were developed with an average size of 140 nm, achieving a high encapsulation efficiency of over 90% for the anticancer drug etoposide. Then, cytotoxicity and apoptosis-inducing effects of these etoposide nanomedicines were assessed in vitro using human cell lines, both cancerous and non-cancerous. The results demonstrated that etoposide nanomedicines exhibited high toxicity and selectively induced apoptosis only in cancerous cells.Next, the biosafety of these nanomedicines in C. elegans, a model organism, was evaluated by measuring survival, body size, and the effect on dividing cells. The findings showed that the nanomedicines had a safer profile than the free etoposide in this model. Notably, nanomedicines exerted etoposide’s antiproliferative effect only in highly proliferative germline cells. Therefore, the developed nanomedicines hold promise as safe drug delivery systems for etoposide, potentially leading to an improved therapeutic index for neuroblastoma treatment. Graphical Abstract
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Lee, Chih-Yung S., Andrea Putnam, Tu Lu, ShuaiXin He, John Paul T. Ouyang und Geraldine Seydoux. „Recruitment of mRNAs to P granules by condensation with intrinsically-disordered proteins“. eLife 9 (24.01.2020). http://dx.doi.org/10.7554/elife.52896.
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RNA granules are protein/RNA condensates. How specific mRNAs are recruited to cytoplasmic RNA granules is not known. Here, we characterize the transcriptome and assembly of P granules, RNA granules in the C. elegans germ plasm. We find that P granules recruit mRNAs by condensation with the disordered protein MEG-3. MEG-3 traps mRNAs into non-dynamic condensates in vitro and binds to ~500 mRNAs in vivo in a sequence-independent manner that favors embryonic mRNAs with low ribosome coverage. Translational stress causes additional mRNAs to localize to P granules and translational activation correlates with P granule exit for two mRNAs coding for germ cell fate regulators. Localization to P granules is not required for translational repression but is required to enrich mRNAs in the germ lineage for robust germline development. Our observations reveal similarities between P granules and stress granules and identify intrinsically-disordered proteins as drivers of RNA condensation during P granule assembly.
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Yao, Baixue, Seth Donoughe, Jonathan Michaux und Edwin Munro. „Modulating RhoA effectors induces transitions to oscillatory and more wavelike RhoA dynamics in C. elegans zygotes.“ Molecular Biology of the Cell, 09.02.2022. http://dx.doi.org/10.1091/mbc.e21-11-0542.
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Pulsatile RhoA dynamics underlie a wide range of cell and tissue behaviors. The circuits that produce these dynamics in different cells share common architectures based on fast positive and delayed negative feedback through F-actin, but they can produce very different spatiotemporal patterns of RhoA activity. However, the underlying causes of this variation remain poorly understood. Here we asked how this variation could arise through modulation of actin network dynamics downstream of active RhoA in early C. elegans embryos. We find that perturbing two RhoA effectors - formin and anillin - induce transitions from non-recurrent focal pulses to either large noisy oscillatory pulses (formin depletion) or noisy oscillatory waves (anillin depletion). In both cases these transitions could be explained by changes in local F-actin levels and depletion dynamics, leading to changes in spatial and temporal patterns of RhoA inhibition. However, the underlying mechanisms for F-actin depletion are distinct, with different dependencies on myosin II activity. Thus, modulating actomyosin network dynamics could shape the spatiotemporal dynamics of RhoA activity for different physiological or morphogenetic functions. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text]