Статті в журналах: "Gene patterning"

1

Kala, A., P. K. Jain, and S. H. Friedman. "Patterning of cells through patterning of biology." Mol. BioSyst. 10, no. 7 (2014): 1689–92. http://dx.doi.org/10.1039/c3mb70587k.

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For the first time, patterns of cells have been constructed by spatially manipulating native gene expression. This control of expression was effected using light activated RNA interference (LARI), a technique in which knockdown of gene expression is modulated through siRNA modified with light cleavable groups.

2

Pyrowolakis, George, Ville Veikkolainen, Nir Yakoby, and Stanislav Y. Shvartsman. "Gene regulation during Drosophila eggshell patterning." Proceedings of the National Academy of Sciences 114, no. 23 (June 5, 2017): 5808–13. http://dx.doi.org/10.1073/pnas.1610619114.

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A common path to the formation of complex 3D structures starts with an epithelial sheet that is patterned by inductive cues that control the spatiotemporal activities of transcription factors. These activities are then interpreted by the cis-regulatory regions of the genes involved in cell differentiation and tissue morphogenesis. Although this general strategy has been documented in multiple developmental contexts, the range of experimental models in which each of the steps can be examined in detail and evaluated in its effect on the final structure remains very limited. Studies of the Drosophila eggshell patterning provide unique insights into the multiscale mechanisms that connect gene regulation and 3D epithelial morphogenesis. Here we review the current understanding of this system, emphasizing how the recent identification of cis-regulatory regions of genes within the eggshell patterning network enables mechanistic analysis of its spatiotemporal dynamics and evolutionary diversification. It appears that cis-regulatory changes can account for only some aspects of the morphological diversity of Drosophila eggshells, such as the prominent differences in the number of the respiratory dorsal appendages. Other changes, such as the appearance of the respiratory eggshell ridges, are caused by changes in the spatial distribution of inductive signals. Both types of mechanisms are at play in this rapidly evolving system, which provides an excellent model of developmental patterning and morphogenesis.

3

Ahringer, J. "Maternal control of a zygotic patterning gene in Caenorhabditis elegans." Development 124, no. 19 (October 1, 1997): 3865–69. http://dx.doi.org/10.1242/dev.124.19.3865.

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The transition from maternal to zygotic gene control is a key process in embryogenesis. Although many maternal effect genes have been studied in the C. elegans embryo, how their activities lead to the positional expression of zygotic patterning genes has not yet been established. Evidence is presented showing that expression of the zygotic patterning gene vab-7 does not depend on cell position or cell contacts, but rather on the production of a C blastomere. Furthermore, pal-1, a caudal homologue with maternal product necessary for the proper development of the C blastomere, is both necessary and sufficient for vab-7 expression. This provides a link between maternal gene activity and zygotic patterning gene expression in C. elegans. The results suggest that zygotic patterning genes might be generally controlled at the level of blastomere fate and not by position.

4

Deyholos, M. K., G. Cordner, D. Beebe, and L. E. Sieburth. "The SCARFACE gene is required for cotyledon and leaf vein patterning." Development 127, no. 15 (August 1, 2000): 3205–13. http://dx.doi.org/10.1242/dev.127.15.3205.

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Mechanisms controlling vein patterning are poorly understood. We describe a recessive Arabidopsis mutant, scarface (sfc), which maps to chromosome 5. sfc mutants have vein pattern defects in cotyledons, leaves, sepals and petals. In contrast to the wild type, in which these organs all have linear veins that are continuous with at least one other vein, in sfc mutants these organs' secondary and tertiary veins are largely replaced by small segments of discontinuous veins, which we call vascular islands. Patterning defects are manifest in cotyledon provascular tissue, suggesting that the patterning defect occurs early in organogenesis. sfc mutants have exaggerated responses to exogenous auxin. Analysis of monopteros (mp(T370)) sfc-1 double mutants suggested that SFC has partially overlapping functions with MP in patterning of both primary and secondary veins.

5

Corbett, Daniel C., Wesley B. Fabyan, Bagrat Grigoryan, Colleen E. O’Connor, Fredrik Johansson, Ivan Batalov, Mary C. Regier, Cole A. DeForest, Jordan S. Miller, and Kelly R. Stevens. "Thermofluidic heat exchangers for actuation of transcription in artificial tissues." Science Advances 6, no. 40 (September 2020): eabb9062. http://dx.doi.org/10.1126/sciadv.abb9062.

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Spatial patterns of gene expression in living organisms orchestrate cell decisions in development, homeostasis, and disease. However, most methods for reconstructing gene patterning in 3D cell culture and artificial tissues are restricted by patterning depth and scale. We introduce a depth- and scale-flexible method to direct volumetric gene expression patterning in 3D artificial tissues, which we call “heat exchangers for actuation of transcription” (HEAT). This approach leverages fluid-based heat transfer from printed networks in the tissues to activate heat-inducible transgenes expressed by embedded cells. We show that gene expression patterning can be tuned both spatially and dynamically by varying channel network architecture, fluid temperature, fluid flow direction, and stimulation timing in a user-defined manner and maintained in vivo. We apply this approach to activate the 3D positional expression of Wnt ligands and Wnt/β-catenin pathway regulators, which are major regulators of development, homeostasis, regeneration, and cancer throughout the animal kingdom.

6

Cooper, Rory L., Alexandre P. Thiery, Alexander G. Fletcher, Daniel J. Delbarre, Liam J. Rasch, and Gareth J. Fraser. "An ancient Turing-like patterning mechanism regulates skin denticle development in sharks." Science Advances 4, no. 11 (November 2018): eaau5484. http://dx.doi.org/10.1126/sciadv.aau5484.

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Vertebrates have a vast array of epithelial appendages, including scales, feathers, and hair. The developmental patterning of these diverse structures can be theoretically explained by Alan Turing’s reaction-diffusion system. However, the role of this system in epithelial appendage patterning of early diverging lineages (compared to tetrapods), such as the cartilaginous fishes, is poorly understood. We investigate patterning of the unique tooth-like skin denticles of sharks, which closely relates to their hydrodynamic and protective functions. We demonstrate through simulation models that a Turing-like mechanism can explain shark denticle patterning and verify this system using gene expression analysis and gene pathway inhibition experiments. This mechanism bears remarkable similarity to avian feather patterning, suggesting deep homology of the system. We propose that a diverse range of vertebrate appendages, from shark denticles to avian feathers and mammalian hair, use this ancient and conserved system, with slight genetic modulation accounting for broad variations in patterning.

7

Solari, F., A. Bateman, and J. Ahringer. "The Caenorhabditis elegans genes egl-27 and egr-1 are similar to MTA1, a member of a chromatin regulatory complex, and are redundantly required for embryonic patterning." Development 126, no. 11 (June 1, 1999): 2483–94. http://dx.doi.org/10.1242/dev.126.11.2483.

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We show here that two functionally redundant Caenorhabditis elegans genes, egl-27 and egr-1, have a fundamental role in embryonic patterning. When both are inactivated, cells in essentially all regions of the embryo fail to be properly organised. Tissue determination and differentiation are unaffected and many zygotic patterning genes are expressed normally, including HOX genes. However, hlh-8, a target of the HOX gene mab-5, is not expressed. egl-27 and egr-1 are members of a gene family that includes MTA1, a human gene with elevated expression in metastatic carcinomas. MTA1 is a component of a protein complex with histone deacetylase and nucleosome remodelling activities. We propose that EGL-27 and EGR-1 function as part of a chromatin regulatory complex required for the function of regional patterning genes.

8

Patel, Nipam H. "The evolution of arthropod segmentation: insights from comparisons of gene expression patterns." Development 1994, Supplement (January 1, 1994): 201–7. http://dx.doi.org/10.1242/dev.1994.supplement.201.

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The comparison of gene expression patterns in a number of insect and crustacean species has led to some insight into the evolution of arthropod patterning mechanisms. These studies have revealed the fundamental nature of the parasegment in a number of organisms, shown that segments can be generated sequentially at the molecular level, and suggested that pair-rule pre-patterning might not be shared by all insects.

9

Özdemir and Gambetta. "The Role of Insulation in Patterning Gene Expression." Genes 10, no. 10 (September 28, 2019): 767. http://dx.doi.org/10.3390/genes10100767.

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Development is orchestrated by regulatory elements that turn genes ON or OFF in precise spatial and temporal patterns. Many safety mechanisms prevent inappropriate action of a regulatory element on the wrong gene promoter. In flies and mammals, dedicated DNA elements (insulators) recruit protein factors (insulator binding proteins, or IBPs) to shield promoters from regulatory elements. In mammals, a single IBP called CCCTC-binding factor (CTCF) is known, whereas genetic and biochemical analyses in Drosophila have identified a larger repertoire of IBPs. How insulators function at the molecular level is not fully understood, but it is currently thought that they fold chromosomes into conformations that affect regulatory element-promoter communication. Here, we review the discovery of insulators and describe their properties. We discuss recent genetic studies in flies and mice to address the question: Is gene insulation important for animal development? Comparing and contrasting observations in these two species reveal that they have different requirements for insulation, but that insulation is a conserved and critical gene regulation strategy.

10

Vakulenko, Sergei, and Ovidiu Radulescu. "Flexible and Robust Patterning by Centralized Gene Networks." Fundamenta Informaticae 118, no. 4 (2012): 345–69. http://dx.doi.org/10.3233/fi-2012-719.

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11

Pearson, Joseph C., Derek Lemons, and William McGinnis. "Modulating Hox gene functions during animal body patterning." Nature Reviews Genetics 6, no. 12 (November 10, 2005): 893–904. http://dx.doi.org/10.1038/nrg1726.

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12

Wu, Xuelin, Vikram Vasisht, David Kosman, John Reinitz, and Stephen Small. "Thoracic Patterning by the Drosophila Gap Gene hunchback." Developmental Biology 237, no. 1 (September 2001): 79–92. http://dx.doi.org/10.1006/dbio.2001.0355.

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13

Tworzydlo, Waclaw, Anna Jablonska, Elzbieta Kisiel, and Szczepan M. Bilinski. "Differing strategies of patterning of follicular cells in higher and lower brachycerans (Diptera: Brachycera)." genesis 43, no. 2 (2005): 49–58. http://dx.doi.org/10.1002/gene.20155.

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14

van Den Akker, E., C. Fromental-Ramain, W. de Graaff, H. Le Mouellic, P. Brulet, P. Chambon, and J. Deschamps. "Axial skeletal patterning in mice lacking all paralogous group 8 Hox genes." Development 128, no. 10 (May 15, 2001): 1911–21. http://dx.doi.org/10.1242/dev.128.10.1911.

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We present a detailed study of the genetic basis of mesodermal axial patterning by paralogous group 8 Hox genes in the mouse. The phenotype of Hoxd8 loss-of-function mutants is presented, and compared with that of Hoxb8- and Hoxc8-null mice. Our analysis of single mutants reveals common features for the Hoxc8 and Hoxd8 genes in patterning lower thoracic and lumbar vertebrae. In the Hoxb8 mutant, more anterior axial regions are affected. The three paralogous Hox genes are expressed up to similar rostral boundaries in the mesoderm, but at levels that strongly vary with the axial position. We find that the axial region affected in each of the single mutants mostly corresponds to the area with the highest level of gene expression. However, analysis of double and triple mutants reveals that lower expression of the other two paralogous genes also plays a patterning role when the mainly expressed gene is defective. We therefore conclude that paralogous group 8 Hox genes are involved in patterning quite an extensive anteroposterior (AP) axial region. Phenotypes of double and triple mutants reveal that Hoxb8, Hoxc8 and Hoxd8 have redundant functions at upper thoracic and sacral levels, including positioning of the hindlimbs. Interestingly, loss of functional Hoxb8 alleles partially rescues the phenotype of Hoxc8- and Hoxc8/Hoxd8-null mutants at lower thoracic and lumbar levels. This suggests that Hoxb8 affects patterning at these axial positions differently from the other paralogous gene products. We conclude that paralogous Hox genes can have a unique role in patterning specific axial regions in addition to their redundant function at other AP levels.

15

Combs, Peter A., and Michael B. Eisen. "Genome-wide measurement of spatial expression in patterning mutants of Drosophila melanogaster." F1000Research 6 (January 12, 2017): 41. http://dx.doi.org/10.12688/f1000research.9720.1.

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Patterning in the Drosophila melanogaster embryo is affected by multiple maternal factors, but the effect of these factors on spatial gene expression has not been systematically analyzed. Here we characterize the effect of the maternal factors Zelda, Hunchback and Bicoid by cryosectioning wildtype and mutant blastoderm stage embryos and sequencing mRNA from each slice. The resulting atlas of spatial gene expression highlights the intersecting roles of these factors in regulating spatial patterns, and serves as a resource for researchers studying spatial patterning in the early embryo. We identify a large number of genes with both expected and unexpected patterning changes, and through integrated analysis of transcription factor binding data identify common themes in genes with complex dependence on these transcription factors.

16

Stathopoulos, Angelike, and Michael Levine. "Linear signaling in the Toll-Dorsal pathway of Drosophila: activated Pelle kinase specifies all threshold outputs of gene expression while the bHLH protein Twist specifies a subset." Development 129, no. 14 (July 15, 2002): 3411–19. http://dx.doi.org/10.1242/dev.129.14.3411.

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Differential activation of the Toll receptor leads to the formation of a broad Dorsal nuclear gradient that specifies at least three patterning thresholds of gene activity along the dorsoventral axis of precellular embryos. We investigate the activities of the Pelle kinase and Twist basic helix-loop-helix (bHLH) transcription factor in transducing Toll signaling. Pelle functions downstream of Toll to release Dorsal from the Cactus inhibitor. Twist is an immediate-early gene that is activated upon entry of Dorsal into nuclei. Transgenes misexpressing Pelle and Twist were introduced into different mutant backgrounds and the patterning activities were visualized using various target genes that respond to different thresholds of Toll-Dorsal signaling. These studies suggest that an anteroposterior gradient of Pelle kinase activity is sufficient to generate all known Toll-Dorsal patterning thresholds and that Twist can function as a gradient morphogen to establish at least two distinct dorsoventral patterning thresholds. We discuss how the Dorsal gradient system can be modified during metazoan evolution and conclude that Dorsal-Twist interactions are distinct from the interplay between Bicoid and Hunchback, which pattern the anteroposterior axis.

17

Sumanas, Saulius, and Stephen C. Ekker. "Xenopus frizzled-7 morphant displays defects in dorsoventral patterning and convergent extension movements during gastrulation." genesis 30, no. 3 (2001): 119–22. http://dx.doi.org/10.1002/gene.1044.

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18

Waschek, James A., Robert A. Casillas, Thinh B. Nguyen, Emanuel M. DiCicco-Bloom, Ellen M. Carpenter, and Williams I. Rodriguez. "Neural tube expression of pituitary adenylate cyclase-activating peptide (PACAP) and receptor: Potential role in patterning and neurogenesis." Proceedings of the National Academy of Sciences 95, no. 16 (August 4, 1998): 9602–7. http://dx.doi.org/10.1073/pnas.95.16.9602.

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Neural tube patterning in vertebrates is controlled in part by locally secreted factors that act in a paracrine manner on nearby cells to regulate proliferation and gene expression. We show here by in situ hybridization that genes for the neuropeptide pituitary adenylate cyclase-activating peptide (PACAP) and one of its high-affinity receptors (PAC1) are widely expressed in the mouse neural tube on embryonic day (E) 10.5. Transcripts for the ligand are present in differentiating neurons in much of the neural tube, whereas the receptor gene is expressed in the underlying ventricular zone, most prominently in the alar region and floor plate. PACAP potently increased cAMP levels more than 20-fold in cultured E10.5 hindbrain neuroepithelial cells, suggesting that PACAP activates protein kinase A (PKA) in the neural tube and might act in the process of patterning. Consistent with this possibility, PACAP down-regulated expression of the sonic hedgehog- and PKA-dependent target gene gli-1 in cultured neuroepithelial cells, concomitant with a decrease in DNA synthesis. PACAP is thus an early inducer of cAMP levels in the embryo and may act in the neural tube during patterning to control cell proliferation and gene expression.

19

Thomson, Travis, and Paul Lasko. "Drosophilatudor is essential for polar granule assembly and pole cell specification, but not for posterior patterning." genesis 40, no. 3 (2004): 164–70. http://dx.doi.org/10.1002/gene.20079.

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20

Shimamura, K., and J. L. Rubenstein. "Inductive interactions direct early regionalization of the mouse forebrain." Development 124, no. 14 (July 15, 1997): 2709–18. http://dx.doi.org/10.1242/dev.124.14.2709.

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The cellular and molecular mechanisms that regulate regional specification of the forebrain are largely unknown. We studied the expression of transcription factors in neural plate explants to identify tissues, and the molecules produced by these tissues, that regulate medial-lateral and local patterning of the prosencephalic neural plate. Molecular properties of the medial neural plate are regulated by the prechordal plate perhaps through the action of Sonic Hedgehog. By contrast, gene expression in the lateral neural plate is regulated by non-neural ectoderm and bone morphogenetic proteins. This suggests that the forebrain employs the same medial-lateral (ventral-dorsal) patterning mechanisms present in the rest of the central nervous system. We have also found that the anterior neural ridge regulates patterning of the anterior neural plate, perhaps through a mechanism that is distinct from those that regulate general medial-lateral patterning. The anterior neural ridge is essential for expression of BF1, a gene encoding a transcription factor required for regionalization and growth of the telencephalic and optic vesicles. In addition, the anterior neural ridge expresses Fgf8, and recombinant FGF8 protein is capable of inducing BF1, suggesting that FGF8 regulates the development of anterolateral neural plate derivatives. Furthermore, we provide evidence that the neural plate is subdivided into distinct anterior-posterior domains that have different responses to the inductive signals from the prechordal plate, Sonic Hedgehog, the anterior neural ridge and FGF8. In sum, these results suggest that regionalization of the forebrain primordia is established by several distinct patterning mechanisms: (1) anterior-posterior patterning creates transverse zones with differential competence within the neural plate, (2) patterning along the medial-lateral axis generates longitudinally aligned domains and (3) local inductive interactions, such as a signal(s) from the anterior neural ridge, further define the regional organization.

21

Styhler, S., A. Nakamura, A. Swan, B. Suter, and P. Lasko. "vasa is required for GURKEN accumulation in the oocyte, and is involved in oocyte differentiation and germline cyst development." Development 125, no. 9 (May 1, 1998): 1569–78. http://dx.doi.org/10.1242/dev.125.9.1569.

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The Drosophila gene vasa is required for pole plasm assembly and function, and also for completion of oogenesis. To investigate the role of vasa in oocyte development, we generated a new null mutation of vasa, which deletes the entire coding region. Analysis of vasa-null ovaries revealed that the gene is involved in the growth of germline cysts. In vasa-null ovaries, germaria are atrophied, and contain far fewer developing cysts than do wild-type germaria; a phenotype similar to, but less severe than, that of a null nanos allele. The null mutant also revealed roles for vasa in oocyte differentiation, anterior-posterior egg chamber patterning, and dorsal-ventral follicle patterning, in addition to its better-characterized functions in posterior embryonic patterning and pole cell specification. The anterior-posterior and dorsal-ventral patterning phenotypes resemble those observed in gurken mutants. vasa-null oocytes fail to efficiently accumulate many localized RNAs, such as Bicaudal-D, orb, oskar, and nanos, but still accumulate gurken RNA. However, GRK accumulation in the oocyte is severely reduced in the absence of vasa function, suggesting a function for VASA in activating gurken translation in wild-type ovaries.

22

Lanctot, C., A. Moreau, M. Chamberland, M. L. Tremblay, and J. Drouin. "Hindlimb patterning and mandible development require the Ptx1 gene." Development 126, no. 9 (May 1, 1999): 1805–10. http://dx.doi.org/10.1242/dev.126.9.1805.

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The restricted expression of the Ptx1 (Pitx1) gene in the posterior half of the lateral plate mesoderm has suggested that it may play a role in specification of posterior structures, in particular, specification of hindlimb identity. Ptx1 is also expressed in the most anterior ectoderm, the stomodeum, and in the first branchial arch. Ptx1 expression overlaps with that of Ptx2 in stomodeum and in posterior left lateral plate mesoderm. We now show that targeted inactivation of the mouse Ptx1 gene severely impairs hindlimb development: the ilium and knee cartilage are absent and the long bones are underdeveloped. Greater reduction of the right femur size in Ptx1 null mice suggests partial compensation by Ptx2 on the left side. The similarly sized tibia and fibula of mutant hindlimbs may be taken to resemble forelimb bones: however, the mutant limb buds appear to have retained their molecular identity as assessed by forelimb expression of Tbx5 and by hindlimb expression of Tbx4, even though Tbx4 expression is decreased in Ptx1 null mice. The hindlimb defects appear to be, at least partly, due to abnormal chondrogenesis. Since the most affected structures derive from the dorsal side of hindlimb buds, the data suggest that Ptx1 is responsible for patterning of these dorsal structures and that as such it may control development of hindlimb-specific features. Ptx1 inactivation also leads to loss of bones derived from the proximal part of the mandibular mesenchyme. The dual role of Ptx1 revealed by the gene knockout may reflect features of the mammalian jaw and hindlimbs that were acquired at a similar time during tetrapod evolution.

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Murray, Stephen A., and Thomas Gridley. "Snail1 Gene Function During Early Embryo Patterning in Mice." Cell Cycle 5, no. 22 (November 2, 2006): 2566–70. http://dx.doi.org/10.4161/cc.5.22.3502.

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24

Loomis, Cynthia A., Esther Harris, Jacques Michaud, Wolfgang Wurst, Mark Hanks, and Alexandra L. Joyner. "The mouse Engrailed-1 gene and ventral limb patterning." Nature 382, no. 6589 (July 1996): 360–63. http://dx.doi.org/10.1038/382360a0.

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Charbonnier, Enrica, Alisa Fuchs, Lily S. Cheung, Mrinal Chayengia, Ville Veikkolainen, Janine Seyfferth, Stanislav Y. Shvartsman, and George Pyrowolakis. "BMP-dependent gene repression cascade in Drosophila eggshell patterning." Developmental Biology 400, no. 2 (April 2015): 258–65. http://dx.doi.org/10.1016/j.ydbio.2015.02.004.

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Cubas, P., and J. Modolell. "The extramacrochaetae gene provides information for sensory organ patterning." EMBO Journal 11, no. 9 (September 1992): 3385–93. http://dx.doi.org/10.1002/j.1460-2075.1992.tb05417.x.

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Diaz-Cuadros, Margarete, Olivier Pourquié, and Ezzat El-Sherif. "Patterning with clocks and genetic cascades: Segmentation and regionalization of vertebrate versus insect body plans." PLOS Genetics 17, no. 10 (October 14, 2021): e1009812. http://dx.doi.org/10.1371/journal.pgen.1009812.

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Oscillatory and sequential processes have been implicated in the spatial patterning of many embryonic tissues. For example, molecular clocks delimit segmental boundaries in vertebrates and insects and mediate lateral root formation in plants, whereas sequential gene activities are involved in the specification of regional identities of insect neuroblasts, vertebrate neural tube, vertebrate limb, and insect and vertebrate body axes. These processes take place in various tissues and organisms, and, hence, raise the question of what common themes and strategies they share. In this article, we review 2 processes that rely on the spatial regulation of periodic and sequential gene activities: segmentation and regionalization of the anterior–posterior (AP) axis of animal body plans. We study these processes in species that belong to 2 different phyla: vertebrates and insects. By contrasting 2 different processes (segmentation and regionalization) in species that belong to 2 distantly related phyla (arthropods and vertebrates), we elucidate the deep logic of patterning by oscillatory and sequential gene activities. Furthermore, in some of these organisms (e.g., the fruit fly Drosophila), a mode of AP patterning has evolved that seems not to overtly rely on oscillations or sequential gene activities, providing an opportunity to study the evolution of pattern formation mechanisms.

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Morton, Sarah U., Paul J. Scherz, Kimberly R. Cordes, Kathryn N. Ivey, Didier Y. R. Stainier, and Deepak Srivastava. "microRNA-138 modulates cardiac patterning during embryonic development." Proceedings of the National Academy of Sciences 105, no. 46 (November 12, 2008): 17830–35. http://dx.doi.org/10.1073/pnas.0804673105.

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Organ patterning during embryonic development requires precise temporal and spatial regulation of protein activity. microRNAs (miRNAs), small noncoding RNAs that typically inhibit protein expression, are broadly important for proper development, but their individual functions during organogenesis are largely unknown. We report that miR-138 is expressed in specific domains in the zebrafish heart and is required to establish appropriate chamber-specific gene expression patterns. Disruption of miR-138 function led to ventricular expansion of gene expression normally restricted to the atrio-ventricular valve region and, ultimately, to disrupted ventricular cardiomyocyte morphology and cardiac function. Temporal-specific knockdown of miR-138 by antagomiRs showed miR-138 function was required during a discrete developmental window, 24–34 h post-fertilization (hpf). miR-138 functioned partially by repressing the retinoic acid synthesis enzyme, aldehyde dehydrogenase-1a2, in the ventricle. This activity was complemented by miR-138-mediated ventricular repression of the gene encoding versican (cspg2), which was positively regulated by retinoic-acid signaling. Our findings demonstrate that miR-138 helps establish discrete domains of gene expression during cardiac morphogenesis by targeting multiple members of a common pathway, and also establish the use of antagomiRs in fish for temporal knockdown of miRNA function.

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Holland, P. W. H., J. Garcia-Fernàndez, L. Z. Holland, N. A. Williams, and N. D. Holland. "The molecular control of spatial patterning in amphioxus." Journal of the Marine Biological Association of the United Kingdom 74, no. 1 (February 1994): 49–60. http://dx.doi.org/10.1017/s0025315400035657.

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The embryology of amphioxus (Chordata: Cephalochordata) has features in common with vertebrate embryology, reflecting a close phylogenetic relationship between the two taxa. Amphioxus differs from vertebrates, however, in having less complex organogenesis and cranial morphogenesis, and less specialization along the anteroposterior body axis. Here we illustrate this by describing the embryology of an amphioxus species, Branchiostoma floridae. To gain further insight into the origins, evolutionary divergence and comparative embryology of these taxa, we are comparing the molecular control of embryonic development in amphioxus and vertebrates. For these analyses, we are focusing on homeobox genes: a diverse multigene family implicated in developmental control in many Metazoa. We report the results of PCR-based experiments which reveal that the amphioxus genome has homeobox genes from several recognized gene classes. The PCR experiments also suggest that amphioxus has fewer ‘Hox’ and ‘Msx’ class homeobox genes than do vertebrates. We suggest, therefore, that amphioxus may be a living descendant from an intermediate stage in the evolution of homeobox gene family complexity, and the complexity of vertebrate developmental control. The pattern of gene expression during embryogenesis has been described for one amphioxus homeobox gene of the Hox class. This gene is primarily expressed in the presumptive neural tube of amphioxus neurulae, later embryos and larvae, in a spatially-restricted manner. The expression data lead us to suggest that Hox genes are involved in the control of spatial patterning in the neural tube of amphioxus; the data are also interpreted as giving insight into possible homology between the amphioxus and vertebrate body plans.

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Smith, K. M., L. Gee, and H. R. Bode. "HyAlx, an aristaless-related gene, is involved in tentacle formation in hydra." Development 127, no. 22 (November 15, 2000): 4743–52. http://dx.doi.org/10.1242/dev.127.22.4743.

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Developmental gradients are known to play important roles in axial patterning in hydra. Current efforts are directed toward elucidating the molecular basis of these gradients. We report the isolation and characterization of HyAlx, an aristaless-related gene in hydra. The expression patterns of the gene in adult hydra, as well as during bud formation, head regeneration and the formation of ectopic head structures along the body column, indicate the gene plays a role in the specification of tissue for tentacle formation. The use of RNAi provides more direct evidence for this conclusion. The different patterns of HyAlx expression during head regeneration and bud formation also provide support for a recent version of a reaction-diffusion model for axial patterning in hydra.

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Schmidt, J., V. Francois, E. Bier, and D. Kimelman. "Drosophila short gastrulation induces an ectopic axis in Xenopus: evidence for conserved mechanisms of dorsal-ventral patterning." Development 121, no. 12 (December 1, 1995): 4319–28. http://dx.doi.org/10.1242/dev.121.12.4319.

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The Spemann organizer has long been recognized as a major source of patterning signals during the gastrula stage of amphibian embryogenesis. More recent evidence has suggested that the ventral side of the embryo also plays an important role in dorsal-ventral patterning during gastrulation through the action of signaling factors such as BMP-4. Bmp-4 is closely related to the Drosophila decapentaplegic (dpp) gene, and like Bmp-4, dpp is excluded from the neurogenic region. Recently we showed that Bmp-4 functions in an analogous role to that of dpp in Drosophila, suggesting that the mechanism of dorsal-ventral patterning in Xenopus and Drosophila embryos may be conserved. To further test this hypothesis, RNA of the Drosophila short gastrulation (sog) gene was injected into Xenopus embryos, since sog has been shown genetically to be an antagonist of dpp function. Overexpression of sog RNA in Xenopus dorsalizes the embryo by expanding neurogenic and dorsal paraxial tissue. When ectopically expressed on the ventral side of the embryo, sog induces a partial secondary axis. In addition, sog partially rescues embryos ventralized by ultraviolet irradiation. Since sog induces many similar changes in gene expression to that caused by truncated BMP receptors, we suggest that sog functions in part by opposing BMP-4 signaling. The recent identification of a possible Xenopus sog homolog, chordin, in conjunction with these results supports the hypothesis that dorsal-ventral patterning mechanisms are conserved between these two species.

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Setton, Emily V. W., and Prashant P. Sharma. "Cooption of an appendage-patterning gene cassette in the head segmentation of arachnids." Proceedings of the National Academy of Sciences 115, no. 15 (March 26, 2018): E3491—E3500. http://dx.doi.org/10.1073/pnas.1720193115.

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The jointed appendages of arthropods have facilitated the spectacular diversity and success of this phylum. Key to the regulation of appendage outgrowth is the Krüppel-like factor (KLF)/specificity protein (Sp) family of zinc finger transcription factors. In the fruit fly, Drosophila melanogaster, the Sp6-9 homolog is activated by Wnt-1/wingless (wg) and establishes ventral appendage (leg) fate. Subsequently, Sp6-9 maintains expression of the axial patterning gene Distal-less (Dll), which promotes limb outgrowth. Intriguingly, in spiders, Dll has been reported to have a derived role as a segmentation gap gene, but the evolutionary origin and regulation of this function are not understood because functional investigations of the appendage-patterning regulatory network are restricted to insects. We tested the evolutionary conservation of the ancestral appendage-patterning network of arthropods with a functional approach in the spider. RNAi-mediated knockdown of the spider Sp6-9 ortholog resulted in diminution or loss of Dll expression and truncation of appendages, as well as loss of the two body segments specified by the early Dll function. In reciprocal experiments, Dll is shown not to be required for Sp6-9 expression. Knockdown of arrow (Wnt-1 coreceptor) disrupted segmentation and appendage development but did not affect the early Sp6-9 expression domain. Ectopic appendages generated in the spider “abdomen” by knockdown of the Hox gene Antennapedia-1 (Antp-1) expressed Sp6-9 comparably to wild-type walking legs. Our results support (i) the evolutionary conservation of an appendage-patterning regulatory network that includes canonical Wnt signaling, Sp6-9, and Dll and (ii) the cooption of the Sp6-9/Dll regulatory cassette in arachnid head segmentation.

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Di Bernardo, M., S. Castagnetti, D. Bellomonte, P. Oliveri, R. Melfi, F. Palla, and G. Spinelli. "Spatially restricted expression of PlOtp, a Paracentrotus lividus orthopedia-related homeobox gene, is correlated with oral ectodermal patterning and skeletal morphogenesis in late-cleavage sea urchin embryos." Development 126, no. 10 (May 15, 1999): 2171–79. http://dx.doi.org/10.1242/dev.126.10.2171.

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Several homeobox genes are expressed in the sea urchin embryo but their roles in development have yet to be elucidated. Of particular interest are homologues of homeobox genes that in mouse and Drosophila are involved in patterning the developing central nervous system (CNS). Here, we report the cloning of an orthopedia (Otp)-related gene from Paracentrotus lividus, PlOtp. Otp is a single copy zygotic gene that presents a unique and highly restricted expression pattern. Transcripts were first detected at the mid-gastrula stage in two pairs of oral ectoderm cells located in a ventrolateral position, overlying primary mesenchyme cell (PMC) clusters. Increases in both transcript abundance and the number of Otp-expressing cells were observed at prism and pluteus stages. Otp transcripts are symmetrically distributed in a few ectodermal cells of the oral field. Labelled cells were observed close to sites of active skeletal rod growth (tips of the budding oral and anal arms), and at the juxtaposition of stomodeum and foregut. Chemicals known to perturb PMC patterning along animal-vegetal and oral-aboral axes altered the pattern of Otp expression. Vegetalization by LiCl caused a shift in Otp-expressing cells toward the animal pole, adjacent to shifted PMC aggregates. Nickel treatment induced expression of the Otp gene in an increased number of ectodermal cells, which adopted a radialized pattern. Finally, ectopic expression of Otp mRNA affected patterning along the oral-aboral axis and caused skeletal abnormalities that resembled those exhibited by nickel-treated embryos. From these results, we conclude that the Otp homeodomain gene is involved in short-range cell signalling within the oral ectoderm for patterning the endoskeleton of the larva through epithelial-mesenchymal interactions.

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Chrystal, Paul W., Curtis R. French, Francesca Jean, Serhiy Havrylov, Suey van Baarle, Ann-Marie Peturson, Pengfei Xu, et al. "The Axenfeld–Rieger Syndrome Gene FOXC1 Contributes to Left–Right Patterning." Genes 12, no. 2 (January 26, 2021): 170. http://dx.doi.org/10.3390/genes12020170.

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Precise spatiotemporal expression of the Nodal-Lefty-Pitx2 cascade in the lateral plate mesoderm establishes the left–right axis, which provides vital cues for correct organ formation and function. Mutations of one cascade constituent PITX2 and, separately, the Forkhead transcription factor FOXC1 independently cause a multi-system disorder known as Axenfeld–Rieger syndrome (ARS). Since cardiac involvement is an established ARS phenotype and because disrupted left–right patterning can cause congenital heart defects, we investigated in zebrafish whether foxc1 contributes to organ laterality or situs. We demonstrate that CRISPR/Cas9-generated foxc1a and foxc1b mutants exhibit abnormal cardiac looping and that the prevalence of cardiac situs defects is increased in foxc1a−/−; foxc1b−/− homozygotes. Similarly, double homozygotes exhibit isomerism of the liver and pancreas, which are key features of abnormal gut situs. Placement of the asymmetric visceral organs relative to the midline was also perturbed by mRNA overexpression of foxc1a and foxc1b. In addition, an analysis of the left–right patterning components, identified in the lateral plate mesoderm of foxc1 mutants, reduced or abolished the expression of the NODAL antagonist lefty2. Together, these data reveal a novel contribution from foxc1 to left–right patterning, demonstrating that this role is sensitive to foxc1 gene dosage, and provide a plausible mechanism for the incidence of congenital heart defects in Axenfeld–Rieger syndrome patients.

35

Broadus, J., and C. Q. Doe. "Evolution of neuroblast identity: seven-up and prospero expression reveal homologous and divergent neuroblast fates in Drosophila and Schistocerca." Development 121, no. 12 (December 1, 1995): 3989–96. http://dx.doi.org/10.1242/dev.121.12.3989.

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In the Drosophila CNS, early neuroblast formation and fate are controlled by the pair-rule class of segmentation genes. The distantly related Schistocerca (grasshopper) embryo has a similar arrangement of neuroblasts, despite lack of known pair-rule gene function. Does divergent pair-rule gene function lead to different neuroblast identities, or can different patterning mechanisms produce homologous neuroblasts? We use four molecular markers to compare Drosophila and Schistocerca neuroblast identity: seven-up, prospero, engrailed, and fushi-tarazu/Dax. In both insects some early-forming neuroblasts share key features of neuroblast identity (position, time of formation, and temporally accurate gene expression); thus, different patterning mechanisms can generate similar neuroblast fates. In contrast, several later-forming neuroblasts show species-specific differences in position and/or gene expression; these neuroblast identities seem to have diverged, suggesting that evolution of the insect central nervous system can occur through changes in embryonic neuroblast identity.

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Hardy, A., M. K. Richardson, P. H. Francis-West, C. Rodriguez, J. C. Izpisua-Belmonte, D. Duprez, and L. Wolpert. "Gene expression, polarising activity and skeletal patterning in reaggregated hind limb mesenchyme." Development 121, no. 12 (December 1, 1995): 4329–37. http://dx.doi.org/10.1242/dev.121.12.4329.

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The developing chick limb has two major signalling centres; the apical ectodermal ridge maintains expression of several important genes and outgrowth of the limb, and the polarising region specifies the pattern of skeletal elements along the anteroposterior axis. We have used reaggregated leg grafts (mesenchyme dissociated into single cells, placed in an ectodermal jacket and grafted to a host) to study patterning in a system where the developmental axes are severely disrupted. Reaggregates from different regions of leg mesenchyme developed correspondingly different digits, giving a system in which skeletal phenotype could be compared with the expression of genes thought to be important in patterning. We found that posterior third and whole leg reaggregates gave rise to different digits, yet expressed the same combination of HoxD, Bmp-2 and shh genes throughout their development. Anterior thirds initially only express the 3′ end of the HoxD cluster but activate the more 5′ members of the cluster sequentially over a period of 48 hours, a period during which Bmp-2 is activated but no shh or Fgf-4 expression could be detected. Our results suggest that there are two independent mechanisms for activating the HoxD complex, one polarising region-dependent and one independent, and that shh expression may not be necessary to maintain outgrowth and patterning once a ridge has been established.

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Araujo, M., M. E. Piedra, M. T. Herrera, M. A. Ros, and M. A. Nieto. "The expression and regulation of chick EphA7 suggests roles in limb patterning and innervation." Development 125, no. 21 (November 1, 1998): 4195–204. http://dx.doi.org/10.1242/dev.125.21.4195.

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Eph receptors and their ligands, the ephrins, have been implicated in early patterning and axon guidance in vertebrate embryos. Members of these families play pivotal roles in the formation of topographic maps in the central nervous system, the formation of brain commissures, and in the guidance of neural crest cells and motor axons through the anterior half of the somites. Here, we report a highly dynamic expression pattern of the chick EphA7 gene in the developing limb. Expression is detected in discrete domains of the dorsal mesenchyme from 3 days of incubation. The expressing cells are adjacent to the routes where axons grow to innervate the limb at several key points: the region of plexus formation, the bifurcation between dorsal and ventral fascicles, and the pathway followed by axons innervating the dorsal muscle mass. These results suggested a role for EphA7 in cell-cell contact-mediated signalling in dorsal limb patterning and/or axon guidance. We carried out experimental manipulations in the chick embryo wing bud to alter the dorsoventral patterning of the limb. The analyses of EphA7 expression and innervation in the operated wings indicate that a signal emanating from the dorsal ectoderm regulates EphA7 in such a way that, in its absence, the wing bud lacks EphA7 expression and shows innervation defects at the regions where the gene was downregulated. EphA7 downregulation in the dorsal mesenchyme after dorsal ectoderm removal is more rapid than that of Lmx-1, the gene known to mediate dorsalisation in response to the ectodermal signal. These results add a new gene to the dorsalisation signalling pathway in the limb. Moreover, they implicate the Eph receptor family in the patterning and innervation of the developing limb, extending its role in axon pathfinding to the distal periphery.

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Sulston, I. A., and K. V. Anderson. "Embryonic patterning mutants of Tribolium castaneum." Development 122, no. 3 (March 1, 1996): 805–14. http://dx.doi.org/10.1242/dev.122.3.805.

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The identification and analysis of genes controlling segmentation in Drosophila melanogaster has opened the way for understanding similarities and differences in mechanisms of segmentation among the insects. Homologues of Drosophila segmentation genes have been cloned and their expression patterns have been analyzed in a variety of insects, revealing that the patterns of expression of many genes are conserved. Conserved expression patterns do not, however, necessarily reflect conserved gene function. To address gene function, we have conducted a screen for mutations that alter embryonic patterning of the beetle, Tribolium castaneum. One of the mutations isolated, godzilla, affects early steps in the segmentation process in the whole animal, like Drosophila pair-rule mutants. Another mutation, jaws, is novel: it caused both a dramatic homeotic transformation in the thorax and first abdominal segment as well as a deletion of most of the segments of the abdomen. In Tribolium and other intermediated germ band insects, the anterior segments of the embryo are determined in the syncytium of the blastoderm, whereas the abdominal segments proliferated in the cellular environment. Both the godzilla and jaws mutations affect segments that are formed in the syncytium differently from those that are formed after cellularization. These regionally specific phenotypes may reflect the different patterning mechanisms that must be employed by the anterior and posterior regions of an intermediated germ insect.

39

Ing-Simmons, Elizabeth, Roshan Vaid, Xin Yang Bing, Michael Levine, Mattias Mannervik, and Juan M. Vaquerizas. "Independence of chromatin conformation and gene regulation during Drosophila dorsoventral patterning." Nature Genetics 53, no. 4 (April 2021): 487–99. http://dx.doi.org/10.1038/s41588-021-00799-x.

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AbstractThe relationship between chromatin organization and gene regulation remains unclear. While disruption of chromatin domains and domain boundaries can lead to misexpression of developmental genes, acute depletion of regulators of genome organization has a relatively small effect on gene expression. It is therefore uncertain whether gene expression and chromatin state drive chromatin organization or whether changes in chromatin organization facilitate cell-type-specific activation of gene expression. Here, using the dorsoventral patterning of the Drosophila melanogaster embryo as a model system, we provide evidence for the independence of chromatin organization and dorsoventral gene expression. We define tissue-specific enhancers and link them to expression patterns using single-cell RNA-seq. Surprisingly, despite tissue-specific chromatin states and gene expression, chromatin organization is largely maintained across tissues. Our results indicate that tissue-specific chromatin conformation is not necessary for tissue-specific gene expression but rather acts as a scaffold facilitating gene expression when enhancers become active.

40

Neuman-Silberberg, F. S., and T. Schupbach. "Dorsoventral axis formation in Drosophila depends on the correct dosage of the gene gurken." Development 120, no. 9 (September 1, 1994): 2457–63. http://dx.doi.org/10.1242/dev.120.9.2457.

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The Drosophila gene gurken participates in a signaling process that occurs between the germ line and the somatic cells (follicle cells) of the ovary. This process is required for correct patterning of the dorsoventral axis of both the egg and the embryo. gurken produces a spatially localized transcript which encodes a TGF-alpha-like molecule (Neuman-Silberberg and Schupbach, Cell 75, 165–174, 1993). Mutations in gurken cause a ventralized phenotype in egg and embryo. To determine whether the gurken gene product plays an instructive role in dorsoventral patterning, we constructed females containing extra copies of a gurken transgene. Such females produce dorsalized eggs and embryos, which is expected if gurken acts as a limiting factor in the dorsoventral patterning process. In addition, the expression pattern of the gene rhomboid in the follicle cells is altered in ovaries of females containing extra copies of gurken. Our results indicate that changing gurken dosage in otherwise wild-type ovaries is sufficient to alter the number of somatic follicle cells directed to the dorsal fate. Therefore the gurken-torpedo signaling process plays an instructive role in oogenesis. It induces dorsal cell fates in the follicle cell epithelium and it controls the production of maternal components that will direct the embryonic dorsoventral pattern after fertilization.

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Andrew, D. J., A. Baig, P. Bhanot, S. M. Smolik, and K. D. Henderson. "The Drosophila dCREB-A gene is required for dorsal/ventral patterning of the larval cuticle." Development 124, no. 1 (January 1, 1997): 181–93. http://dx.doi.org/10.1242/dev.124.1.181.

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We report on the characterization of the first loss-of-function mutation in a Drosophila CREB gene, dCREB-A. In the epidermis, dCREB-A is required for patterning cuticular structures on both dorsal and ventral surfaces since dCREB-A mutant larvae have only lateral structures around the entire circumference of each segment. Based on results from epistasis tests with known dorsal/ventral patterning genes, we propose that dCREB-A encodes a transcription factor that functions near the end of both the DPP- and SPI-signaling cascades to translate the corresponding extracellular signals into changes in gene expression. The lateralizing phenotype of dCREB-A mutants reveals a much broader function for CREB proteins than previously thought.

42

Rahimi, Neta, Shari Carmon, Inna Averbukh, Farzaneh Khajouei, Saurabh Sinha, Eyal D. Schejter, Naama Barkai, and Ben-Zion Shilo. "Global shape of Toll activation is determined by wntD enhancer properties." Proceedings of the National Academy of Sciences 117, no. 3 (January 3, 2020): 1552–58. http://dx.doi.org/10.1073/pnas.1918268117.

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Buffering variability in morphogen distribution is essential for reproducible patterning. A theoretically proposed class of mechanisms, termed “distal pinning,” achieves robustness by combining local sensing of morphogen levels with global modulation of gradient spread. Here, we demonstrate a critical role for morphogen sensing by a gene enhancer, which ultimately determines the final global distribution of the morphogen and enables reproducible patterning. Specifically, we show that, while the pattern of Toll activation in the early Drosophila embryo is robust to gene dosage of its locally produced regulator, WntD, it is sensitive to a single-nucleotide change in the wntD enhancer. Thus, enhancer properties of locally produced WntD directly impinge on the global morphogen profile.

43

Pultz, M. A., J. N. Pitt, and N. M. Alto. "Extensive zygotic control of the anteroposterior axis in the wasp Nasonia vitripennis." Development 126, no. 4 (February 15, 1999): 701–10. http://dx.doi.org/10.1242/dev.126.4.701.

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Insect axis formation is best understood in Drosophila melanogaster, where rapid anteroposterior patterning of zygotic determinants is directed by maternal gene products. The earliest zygotic control is by gap genes, which determine regions of several contiguous segments and are largely conserved in insects. We have asked genetically whether early zygotic patterning genes control similar anteroposterior domains in the parasitoid wasp Nasonia vitripennis as in Drosophila. Nasonia is advantageous for identifying and studying recessive zygotic lethal mutations because unfertilized eggs develop as males while fertilized eggs develop as females. Here we describe recessive zygotic mutations identifying three Nasonia genes: head only mutant embryos have posterior defects, resembling loss of both maternal and zygotic Drosophila caudal function; headless mutant embryos have anterior and posterior gap defects, resembling loss of both maternal and zygotic Drosophila hunchback function; squiggy mutant embryos develop only four full trunk segments, a phenotype more severe than those caused by lack of Drosophila maternal or zygotic terminal gene functions. These results indicate greater dependence on the zygotic genome to control early patterning in Nasonia than in the fly.

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Smith, Kelly A., and Veronica Uribe. "Getting to the Heart of Left–Right Asymmetry: Contributions from the Zebrafish Model." Journal of Cardiovascular Development and Disease 8, no. 6 (June 4, 2021): 64. http://dx.doi.org/10.3390/jcdd8060064.

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The heart is laterally asymmetric. Not only is it positioned on the left side of the body but the organ itself is asymmetric. This patterning occurs across scales: at the organism level, through left–right axis patterning; at the organ level, where the heart itself exhibits left–right asymmetry; at the cellular level, where gene expression, deposition of matrix and proteins and cell behaviour are asymmetric; and at the molecular level, with chirality of molecules. Defective left–right patterning has dire consequences on multiple organs; however, mortality and morbidity arising from disrupted laterality is usually attributed to complex cardiac defects, bringing into focus the particulars of left–right patterning of the heart. Laterality defects impact how the heart integrates and connects with neighbouring organs, but the anatomy of the heart is also affected because of its asymmetry. Genetic studies have demonstrated that cardiac asymmetry is influenced by left–right axis patterning and yet the heart also possesses intrinsic laterality, reinforcing the patterning of this organ. These inputs into cardiac patterning are established at the very onset of left–right patterning (formation of the left–right organiser) and continue through propagation of left–right signals across animal axes, asymmetric differentiation of the cardiac fields, lateralised tube formation and asymmetric looping morphogenesis. In this review, we will discuss how left–right asymmetry is established and how that influences subsequent asymmetric development of the early embryonic heart. In keeping with the theme of this issue, we will focus on advancements made through studies using the zebrafish model and describe how its use has contributed considerable knowledge to our understanding of the patterning of the heart.

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Vincent, A., J. T. Blankenship, and E. Wieschaus. "Integration of the head and trunk segmentation systems controls cephalic furrow formation in Drosophila." Development 124, no. 19 (October 1, 1997): 3747–54. http://dx.doi.org/10.1242/dev.124.19.3747.

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Genetic and molecular analyses of patterning of the Drosophila embryo have shown that the process of segmentation of the head is fundamentally different from the process of segmentation of the trunk. The cephalic furrow (CF), one of the first morphological manifestations of the patterning process, forms at the juxtaposition of these two patterning systems. We report here that the initial step in CF formation is a change in shape and apical positioning of a single row of cells. The anteroposterior position of these initiator cells may be defined by the overlapping expression of the head gap gene buttonhead (btd) and the primary pair-rule gene even-skipped (eve). Re-examination of the btd and eve phenotypes in live embryos indicated that both genes are required for CF formation. Further, Eve expression in initiator cells was found to be dependent upon btd activity. The control of eve expression by btd in these cells is the first indication of a new level of integrated regulation that interfaces the head and trunk segmentation systems. In conjunction with previous data on the btd and eve embryonic phenotypes, our results suggest that interaction between these two genes both controls initiation of a specific morphogenetic movement that separates two morphogenetic fields and contributes to patterning the hinge region that demarcates the procephalon from the segmented germ band.

46

Cleaver, O., and P. A. Krieg. "VEGF mediates angioblast migration during development of the dorsal aorta in Xenopus." Development 125, no. 19 (October 1, 1998): 3905–14. http://dx.doi.org/10.1242/dev.125.19.3905.

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Angioblasts are precursor cells of the vascular endothelium which organize into the primitive blood vessels during embryogenesis. The molecular mechanisms underlying patterning of the embryonic vasculature remain unclear. Mutational analyses of the receptor tyrosine kinase flk-1 and its ligand vascular endothelial growth factor, VEGF, indicate that these molecules are critical for vascular development. Targeted ablation of the flk-1 gene results in complete failure of blood and vascular development (F. Shalaby et al. (1995) Nature 376, 62–66), while targeted ablation of the VEGF gene results in gross abnormalities in vascular patterning (P. Carmeliet et al. (1996) Nature 380, 435–439; N. Ferrara et al. (1996) Nature 380, 439–442). Here we report a role for VEGF in patterning the dorsal aorta of the Xenopus embryo. We show that the diffusible form of VEGF is expressed by the hypochord, which lies at the embryonic midline immediately dorsal to the location of the future dorsal aorta. We find that, initially, no flk-1-expressing angioblasts are present at this location, but that during subsequent development, angioblasts migrate from the lateral plate mesoderm to the midline where they form a single dorsal aorta. We have demonstrated that VEGF can act as a chemoattractant for angioblasts by ectopic expression of VEGF in the embryo. These results strongly suggest that localized sources of VEGF play a role in patterning the embryonic vasculature.

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Moon, A. M., A. M. Boulet, and M. R. Capecchi. "Normal limb development in conditional mutants of Fgf4." Development 127, no. 5 (March 1, 2000): 989–96. http://dx.doi.org/10.1242/dev.127.5.989.

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Fibroblast growth factors (FGFs) mediate multiple developmental signals in vertebrates. Several of these factors are expressed in limb bud structures that direct patterning of the limb. FGF4 is produced in the apical ectodermal ridge (AER) where it is hypothesized to provide mitogenic and morphogenic signals to the underlying mesenchyme that regulate normal limb development. Mutation of this gene in the germline of mice results in early embryonic lethality, preventing subsequent evaluation of Fgf4 function in the AER. A conditional mutant of Fgf4, based on site-specific Cre/loxP-mediated excision of the gene, allowed us to bypass embryonic lethality and directly test the role of FGF4 during limb development in living murine embryos. This conditional mutation was designed so that concomitant with inactivation of the Fgf4 gene by excision of all Fgf4-coding sequences, a reporter gene was activated in Fgf4-expressing cells, allowing assessment of the site-specific recombination reaction. Although a large body of evidence led us to predict that ablation of Fgf4 gene function in the AER of developing mice would result in abnormal limb outgrowth and patterning, we found that Fgf4 conditional mutants had normal limbs. Furthermore, expression patterns of Shh, Bmp2, Fgf8 and Fgf10 were normal in the limb buds of the conditional mutants. These findings indicate that the previously proposed FGF4-SHH feedback loop is not essential for coordination of murine limb outgrowth and patterning. We suggest that some of the roles currently attributed to FGF4 during early vertebrate limb development may be performed by other AER factors in vivo.

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Perkins, Melinda Liu. "Implications of diffusion and time-varying morphogen gradients for the dynamic positioning and precision of bistable gene expression boundaries." PLOS Computational Biology 17, no. 6 (June 1, 2021): e1008589. http://dx.doi.org/10.1371/journal.pcbi.1008589.

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The earliest models for how morphogen gradients guide embryonic patterning failed to account for experimental observations of temporal refinement in gene expression domains. Following theoretical and experimental work in this area, dynamic positional information has emerged as a conceptual framework to discuss how cells process spatiotemporal inputs into downstream patterns. Here, we show that diffusion determines the mathematical means by which bistable gene expression boundaries shift over time, and therefore how cells interpret positional information conferred from morphogen concentration. First, we introduce a metric for assessing reproducibility in boundary placement or precision in systems where gene products do not diffuse, but where morphogen concentrations are permitted to change in time. We show that the dynamics of the gradient affect the sensitivity of the final pattern to variation in initial conditions, with slower gradients reducing the sensitivity. Second, we allow gene products to diffuse and consider gene expression boundaries as propagating wavefronts with velocity modulated by local morphogen concentration. We harness this perspective to approximate a PDE model as an ODE that captures the position of the boundary in time, and demonstrate the approach with a preexisting model for Hunchback patterning in fruit fly embryos. We then propose a design that employs antiparallel morphogen gradients to achieve accurate boundary placement that is robust to scaling. Throughout our work we draw attention to tradeoffs among initial conditions, boundary positioning, and the relative timescales of network and gradient evolution. We conclude by suggesting that mathematical theory should serve to clarify not just our quantitative, but also our intuitive understanding of patterning processes.

49

Fietz, Michael J., Jean-Paul Concordet, Robert Barbosa, Randy Johnson, Stefan Krauss, Andrew P. McMahon, Cliff Tabin, and Philip W. Ingham. "The hedgehog gene family in Drosophila and vertebrate development." Development 1994, Supplement (January 1, 1994): 43–51. http://dx.doi.org/10.1242/dev.1994.supplement.43.

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The segment polarity gene hedgehog plays a central role in cell patterning during embryonic and post-embryonic development of the dipteran, Drosophila melanogaster. Recent studies have identified a family of hedgehog related genes in vertebrates; one of these, Sonic hedgehog is implicated in positional signalling processes that show interesting similarities with those controlled by its Drosophila homologue.

50

Bejsovec, A., and A. Martinez Arias. "Roles of wingless in patterning the larval epidermis of Drosophila." Development 113, no. 2 (October 1, 1991): 471–85. http://dx.doi.org/10.1242/dev.113.2.471.

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The larval epidermis of Drosophila shows a stereotyped segmentally repeating pattern of cuticular structures. Mutants deficient for the wingless gene product show highly disrupted patterning of the larval cuticle. We have manipulated expression of the wg gene product to assess its role in this patterning process. We present evidence for four distinct phases of wg function in epidermal cells: (1) an early requirement in engrailed-expressing cells to establish and maintain stable expression of en, (2) a discrete period when wg and en gene products act in concert to generate positional values in the anterior portion of the ventral segment and all values of the dorsal and lateral epidermis, (3) a progressive function (dependent on prior interaction with the en-expressing cells) in conferring positional values to cells within the posterior portion of the segment, and (4) a late continuous requirement for maintaining some ventral positional values.

Статті в журналах з теми "Gene patterning"

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