Pub Date : 2020-01-01DOI: 10.1101/2020.04.08.033092
K. Bellec, M. Pinot, I. Gicquel, R. Le Borgne
ABSTRACT Drosophila sensory organ precursors divide asymmetrically to generate pIIa/pIIb cells, the identity of which relies on activation of Notch at cytokinesis. Although Notch is present apically and basally relative to the midbody at the pIIa-pIIb interface, the basal pool of Notch is reported to be the main contributor for Notch activation in the pIIa cell. Intra-lineage signalling requires appropriate apico-basal targeting of Notch, its ligand Delta and its trafficking partner Sanpodo. We have previously reported that AP-1 and Stratum regulate the trafficking of Notch and Sanpodo from the trans-Golgi network to the basolateral membrane. Loss of AP-1 or Stratum caused mild Notch gain-of-function phenotypes. Here, we report that their concomitant loss results in a penetrant Notch gain-of-function phenotype, indicating that they control parallel pathways. Although unequal partitioning of cell fate determinants and cell polarity were unaffected, we observed increased amounts of signalling-competent Notch as well as Delta and Sanpodo at the apical pIIa-pIIb interface, at the expense of the basal pool of Notch. We propose that AP-1 and Stratum operate in parallel pathways to localize Notch and control where receptor activation takes place. Summary: The Notch pathway activation relies on the correct localization of the Notch signalling actors. We report that AP-1 and Stratum ensure the basolateral targeting of Notch during asymmetric cell division.
{"title":"The Clathrin adaptor AP-1 and Stratum act in parallel pathways to control Notch activation in Drosophila sensory organ precursors cells","authors":"K. Bellec, M. Pinot, I. Gicquel, R. Le Borgne","doi":"10.1101/2020.04.08.033092","DOIUrl":"https://doi.org/10.1101/2020.04.08.033092","url":null,"abstract":"ABSTRACT Drosophila sensory organ precursors divide asymmetrically to generate pIIa/pIIb cells, the identity of which relies on activation of Notch at cytokinesis. Although Notch is present apically and basally relative to the midbody at the pIIa-pIIb interface, the basal pool of Notch is reported to be the main contributor for Notch activation in the pIIa cell. Intra-lineage signalling requires appropriate apico-basal targeting of Notch, its ligand Delta and its trafficking partner Sanpodo. We have previously reported that AP-1 and Stratum regulate the trafficking of Notch and Sanpodo from the trans-Golgi network to the basolateral membrane. Loss of AP-1 or Stratum caused mild Notch gain-of-function phenotypes. Here, we report that their concomitant loss results in a penetrant Notch gain-of-function phenotype, indicating that they control parallel pathways. Although unequal partitioning of cell fate determinants and cell polarity were unaffected, we observed increased amounts of signalling-competent Notch as well as Delta and Sanpodo at the apical pIIa-pIIb interface, at the expense of the basal pool of Notch. We propose that AP-1 and Stratum operate in parallel pathways to localize Notch and control where receptor activation takes place. Summary: The Notch pathway activation relies on the correct localization of the Notch signalling actors. We report that AP-1 and Stratum ensure the basolateral targeting of Notch during asymmetric cell division.","PeriodicalId":77105,"journal":{"name":"Development (Cambridge, England). Supplement","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77985167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N. Staudt, F. Giger, Triona Fielding, J. A. Hutt, Isabelle Foucher, Victoria Snowden, Agathe Hellich, C. Kiecker, C. Houart
ABSTRACT The embryonic development of the pineal organ, a neuroendocrine gland on top of the diencephalon, remains enigmatic. Classic fate-mapping studies suggested that pineal progenitors originate from the lateral border of the anterior neural plate. We show here, using gene expression and fate mapping/lineage tracing in zebrafish, that pineal progenitors originate, at least in part, from the non-neural ectoderm. Gene expression in chick indicates that this non-neural origin of pineal progenitors is conserved in amniotes. Genetic repression of placodal, but not neural crest, cell fate results in pineal hypoplasia in zebrafish, while mis-expression of transcription factors known to specify placodal identity during gastrulation promotes the formation of ectopic pineal progenitors. We also demonstrate that fibroblast growth factors (FGFs) position the pineal progenitor domain within the non-neural border by repressing pineal fate and that the Otx transcription factors promote pinealogenesis by inhibiting this FGF activity. The non-neural origin of the pineal organ reveals an underlying similarity in the formation of the pineal and pituitary glands, and suggests that all CNS neuroendocrine organs may require a non-neural contribution to form neurosecretory cells. Highlighted Article: Gene expression and fate mapping/lineage tracing in zebrafish reveals that the pineal organ develops from the non-neural pre-placodal ectoderm under the control of FGF signalling.
{"title":"Pineal progenitors originate from a non-neural territory limited by FGF signalling","authors":"N. Staudt, F. Giger, Triona Fielding, J. A. Hutt, Isabelle Foucher, Victoria Snowden, Agathe Hellich, C. Kiecker, C. Houart","doi":"10.1242/dev.171405","DOIUrl":"https://doi.org/10.1242/dev.171405","url":null,"abstract":"ABSTRACT The embryonic development of the pineal organ, a neuroendocrine gland on top of the diencephalon, remains enigmatic. Classic fate-mapping studies suggested that pineal progenitors originate from the lateral border of the anterior neural plate. We show here, using gene expression and fate mapping/lineage tracing in zebrafish, that pineal progenitors originate, at least in part, from the non-neural ectoderm. Gene expression in chick indicates that this non-neural origin of pineal progenitors is conserved in amniotes. Genetic repression of placodal, but not neural crest, cell fate results in pineal hypoplasia in zebrafish, while mis-expression of transcription factors known to specify placodal identity during gastrulation promotes the formation of ectopic pineal progenitors. We also demonstrate that fibroblast growth factors (FGFs) position the pineal progenitor domain within the non-neural border by repressing pineal fate and that the Otx transcription factors promote pinealogenesis by inhibiting this FGF activity. The non-neural origin of the pineal organ reveals an underlying similarity in the formation of the pineal and pituitary glands, and suggests that all CNS neuroendocrine organs may require a non-neural contribution to form neurosecretory cells. Highlighted Article: Gene expression and fate mapping/lineage tracing in zebrafish reveals that the pineal organ develops from the non-neural pre-placodal ectoderm under the control of FGF signalling.","PeriodicalId":77105,"journal":{"name":"Development (Cambridge, England). Supplement","volume":"76 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78716536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
D. S. Osório, Fung-Yi Chan, J. Saramago, J. Leite, A. M. Silva, A. F. Sobral, R. Gassmann, A. Carvalho
ABSTRACT Cytokinesis in animal cells requires the assembly and constriction of a contractile actomyosin ring. Non-muscle myosin II is essential for cytokinesis, but the role of its motor activity remains unclear. Here, we examine cytokinesis in C. elegans embryos expressing non-muscle myosin motor mutants generated by genome editing. Two non-muscle motor-dead myosins capable of binding F-actin do not support cytokinesis in the one-cell embryo, and two partially motor-impaired myosins delay cytokinesis and render rings more sensitive to reduced myosin levels. Further analysis of myosin mutants suggests that it is myosin motor activity, and not the ability of myosin to crosslink F-actin, that drives the alignment and compaction of F-actin bundles during contractile ring assembly, and that myosin motor activity sets the pace of contractile ring constriction. We conclude that myosin motor activity is required at all stages of cytokinesis. Finally, characterization of the corresponding motor mutations in C. elegans major muscle myosin shows that motor activity is required for muscle contraction but is dispensable for F-actin organization in adult muscles. This article has an associated ‘The people behind the papers’ interview. Highlighted Article: The motor activity of non-muscle myosin II is essential for cytokinesis and contributes to all stages of the process in C. elegans embryos.
{"title":"Crosslinking activity of non-muscle myosin II is not sufficient for embryonic cytokinesis in C. elegans","authors":"D. S. Osório, Fung-Yi Chan, J. Saramago, J. Leite, A. M. Silva, A. F. Sobral, R. Gassmann, A. Carvalho","doi":"10.1242/dev.179150","DOIUrl":"https://doi.org/10.1242/dev.179150","url":null,"abstract":"ABSTRACT Cytokinesis in animal cells requires the assembly and constriction of a contractile actomyosin ring. Non-muscle myosin II is essential for cytokinesis, but the role of its motor activity remains unclear. Here, we examine cytokinesis in C. elegans embryos expressing non-muscle myosin motor mutants generated by genome editing. Two non-muscle motor-dead myosins capable of binding F-actin do not support cytokinesis in the one-cell embryo, and two partially motor-impaired myosins delay cytokinesis and render rings more sensitive to reduced myosin levels. Further analysis of myosin mutants suggests that it is myosin motor activity, and not the ability of myosin to crosslink F-actin, that drives the alignment and compaction of F-actin bundles during contractile ring assembly, and that myosin motor activity sets the pace of contractile ring constriction. We conclude that myosin motor activity is required at all stages of cytokinesis. Finally, characterization of the corresponding motor mutations in C. elegans major muscle myosin shows that motor activity is required for muscle contraction but is dispensable for F-actin organization in adult muscles. This article has an associated ‘The people behind the papers’ interview. Highlighted Article: The motor activity of non-muscle myosin II is essential for cytokinesis and contributes to all stages of the process in C. elegans embryos.","PeriodicalId":77105,"journal":{"name":"Development (Cambridge, England). Supplement","volume":"78 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79314336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daniel Krueger, Emiliano Izquierdo, Ranjith Viswanathan, Jonas Hartmann, Cristina Pallares Cartes, S. De Renzis
ABSTRACT The development of multicellular organisms is controlled by highly dynamic molecular and cellular processes organized in spatially restricted patterns. Recent advances in optogenetics are allowing protein function to be controlled with the precision of a pulse of laser light in vivo, providing a powerful new tool to perturb developmental processes at a wide range of spatiotemporal scales. In this Primer, we describe the most commonly used optogenetic tools, their application in developmental biology and in the nascent field of synthetic morphogenesis. Summary: Optogenetics allows the control of protein function with the precision of a pulse of laser light. This Primer gives an overview of the most commonly used optogenetic tools and their application in developmental biology.
{"title":"Principles and applications of optogenetics in developmental biology","authors":"Daniel Krueger, Emiliano Izquierdo, Ranjith Viswanathan, Jonas Hartmann, Cristina Pallares Cartes, S. De Renzis","doi":"10.1242/dev.175067","DOIUrl":"https://doi.org/10.1242/dev.175067","url":null,"abstract":"ABSTRACT The development of multicellular organisms is controlled by highly dynamic molecular and cellular processes organized in spatially restricted patterns. Recent advances in optogenetics are allowing protein function to be controlled with the precision of a pulse of laser light in vivo, providing a powerful new tool to perturb developmental processes at a wide range of spatiotemporal scales. In this Primer, we describe the most commonly used optogenetic tools, their application in developmental biology and in the nascent field of synthetic morphogenesis. Summary: Optogenetics allows the control of protein function with the precision of a pulse of laser light. This Primer gives an overview of the most commonly used optogenetic tools and their application in developmental biology.","PeriodicalId":77105,"journal":{"name":"Development (Cambridge, England). Supplement","volume":"220 1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86253753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elisavet Tika, Marielle Ousset, Anne Dannau, C. Blanpain
ABSTRACT The prostate is formed by a branched glandular epithelium composed of basal cells (BCs) and luminal cells (LCs). Multipotent and unipotent stem cells (SCs) mediate the initial steps of prostate development whereas BCs and LCs are self-sustained in adult mice by unipotent lineage-restricted SCs. The spatiotemporal regulation of SC fate and the switch from multipotency to unipotency remain poorly characterised. Here, by combining lineage tracing, whole-tissue imaging, clonal analysis and proliferation kinetics, we uncover the cellular dynamics that orchestrate prostate postnatal development in mouse. We found that at an early stage of development multipotent basal SCs are located throughout the epithelium and are progressively restricted at the distal tip of the ducts, where, together with their progeny, they establish the different branches and the final structure of prostate. In contrast, pubertal development is mediated by unipotent lineage-restricted SCs. Our results uncover the spatiotemporal regulation of the switch from multipotency to unipotency during prostate development. Highlighted Article: A combination of lineage tracing and whole-mount imaging uncovers how the multipotency of basal stem cells is regulated during postnatal prostate development in mouse.
{"title":"Spatiotemporal regulation of multipotency during prostate development","authors":"Elisavet Tika, Marielle Ousset, Anne Dannau, C. Blanpain","doi":"10.1242/dev.180224","DOIUrl":"https://doi.org/10.1242/dev.180224","url":null,"abstract":"ABSTRACT The prostate is formed by a branched glandular epithelium composed of basal cells (BCs) and luminal cells (LCs). Multipotent and unipotent stem cells (SCs) mediate the initial steps of prostate development whereas BCs and LCs are self-sustained in adult mice by unipotent lineage-restricted SCs. The spatiotemporal regulation of SC fate and the switch from multipotency to unipotency remain poorly characterised. Here, by combining lineage tracing, whole-tissue imaging, clonal analysis and proliferation kinetics, we uncover the cellular dynamics that orchestrate prostate postnatal development in mouse. We found that at an early stage of development multipotent basal SCs are located throughout the epithelium and are progressively restricted at the distal tip of the ducts, where, together with their progeny, they establish the different branches and the final structure of prostate. In contrast, pubertal development is mediated by unipotent lineage-restricted SCs. Our results uncover the spatiotemporal regulation of the switch from multipotency to unipotency during prostate development. Highlighted Article: A combination of lineage tracing and whole-mount imaging uncovers how the multipotency of basal stem cells is regulated during postnatal prostate development in mouse.","PeriodicalId":77105,"journal":{"name":"Development (Cambridge, England). Supplement","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75275800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Y. Sato, Lennart Hilbert, H. Oda, Yinan Wan, John M. Heddleston, T. Chew, V. Zaburdaev, Philipp J. Keller, T. Lionnet, N. Vastenhouw, H. Kimura
ABSTRACT Histone post-translational modifications are key gene expression regulators, but their rapid dynamics during development remain difficult to capture. We applied a Fab-based live endogenous modification labeling technique to monitor the changes in histone modification levels during zygotic genome activation (ZGA) in living zebrafish embryos. Among various histone modifications, H3 Lys27 acetylation (H3K27ac) exhibited most drastic changes, accumulating in two nuclear foci in the 64- to 1k-cell-stage embryos. The elongating form of RNA polymerase II, which is phosphorylated at Ser2 in heptad repeats within the C-terminal domain (RNAP2 Ser2ph), and miR-430 transcripts were also concentrated in foci closely associated with H3K27ac. When treated with α-amanitin to inhibit transcription or JQ-1 to inhibit binding of acetyl-reader proteins, H3K27ac foci still appeared but RNAP2 Ser2ph and miR-430 morpholino were not concentrated in foci, suggesting that H3K27ac precedes active transcription during ZGA. We anticipate that the method presented here could be applied to a variety of developmental processes in any model and non-model organisms. Summary: FabLEM, an endogenous labeling technique that uses modification-specific antigen-binding fragments, is used to examine changes in histone modification levels and transcription during zygotic genome activation in live zebrafish embryos.
{"title":"Histone H3K27 acetylation precedes active transcription during zebrafish zygotic genome activation as revealed by live-cell analysis","authors":"Y. Sato, Lennart Hilbert, H. Oda, Yinan Wan, John M. Heddleston, T. Chew, V. Zaburdaev, Philipp J. Keller, T. Lionnet, N. Vastenhouw, H. Kimura","doi":"10.1242/dev.179127","DOIUrl":"https://doi.org/10.1242/dev.179127","url":null,"abstract":"ABSTRACT Histone post-translational modifications are key gene expression regulators, but their rapid dynamics during development remain difficult to capture. We applied a Fab-based live endogenous modification labeling technique to monitor the changes in histone modification levels during zygotic genome activation (ZGA) in living zebrafish embryos. Among various histone modifications, H3 Lys27 acetylation (H3K27ac) exhibited most drastic changes, accumulating in two nuclear foci in the 64- to 1k-cell-stage embryos. The elongating form of RNA polymerase II, which is phosphorylated at Ser2 in heptad repeats within the C-terminal domain (RNAP2 Ser2ph), and miR-430 transcripts were also concentrated in foci closely associated with H3K27ac. When treated with α-amanitin to inhibit transcription or JQ-1 to inhibit binding of acetyl-reader proteins, H3K27ac foci still appeared but RNAP2 Ser2ph and miR-430 morpholino were not concentrated in foci, suggesting that H3K27ac precedes active transcription during ZGA. We anticipate that the method presented here could be applied to a variety of developmental processes in any model and non-model organisms. Summary: FabLEM, an endogenous labeling technique that uses modification-specific antigen-binding fragments, is used to examine changes in histone modification levels and transcription during zygotic genome activation in live zebrafish embryos.","PeriodicalId":77105,"journal":{"name":"Development (Cambridge, England). Supplement","volume":"134 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76871283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Neha Ghosh, Asif Bakshi, Risha Khandelwal, Sriivatsan G. Rajan, R. Joshi
ABSTRACT Highly conserved DM domain-containing transcription factors (Doublesex/MAB-3/DMRT1) are responsible for generating sexually dimorphic features. In the Drosophila central nervous system, a set of Doublesex (Dsx)-expressing neuroblasts undergo apoptosis in females whereas their male counterparts proliferate and give rise to serotonergic neurons crucial for adult mating behaviour. Our study demonstrates that the female-specific isoform of Dsx collaborates with Hox gene Abdominal-B (Abd-B) to bring about this apoptosis. Biochemical results suggest that proteins AbdB and Dsx interact through their highly conserved homeodomain and DM domain, respectively. This interaction is translated into a cooperative binding of the two proteins on the apoptotic enhancer in the case of females but not in the case of males, resulting in female-specific activation of apoptotic genes. The capacity of AbdB to use the sex-specific isoform of Dsx as a cofactor underlines the possibility that these two classes of protein are capable of cooperating in selection and regulation of target genes in a tissue- and sex-specific manner. We propose that this interaction could be a common theme in generating sexual dimorphism in different tissues across different species. Highlighted Article: Drosophila DoublesexF collaborates with Abdominal-B to generate a sexually dimorphic central nervous system.
高度保守的含有DM结构域的转录因子(doubesex /MAB-3/DMRT1)负责产生两性二态特征。在果蝇的中枢神经系统中，一组表达双性(Dsx)的神经母细胞在雌性中经历凋亡，而它们的雄性对应细胞增殖并产生对成年交配行为至关重要的血清素能神经元。我们的研究表明，Dsx的女性特异性亚型与Hox基因腹部- b (Abd-B)协同导致这种细胞凋亡。生化结果表明，AbdB和Dsx蛋白分别通过高度保守的同源结构域和DM结构域相互作用。这种相互作用在雌性中转化为两种蛋白在凋亡增强子上的合作结合，而在雄性中则不然，导致雌性特异性的凋亡基因激活。AbdB利用Dsx的性别特异性异构体作为辅助因子的能力强调了这两类蛋白能够以组织和性别特异性的方式合作选择和调节靶基因的可能性。我们认为这种相互作用可能是在不同物种的不同组织中产生两性异形的共同主题。重点文章:双歧果蝇f与腹部b协同产生两性二态的中枢神经系统。
{"title":"The Hox gene Abdominal-B uses DoublesexF as a cofactor to promote neuroblast apoptosis in the Drosophila central nervous system","authors":"Neha Ghosh, Asif Bakshi, Risha Khandelwal, Sriivatsan G. Rajan, R. Joshi","doi":"10.1242/dev.175158","DOIUrl":"https://doi.org/10.1242/dev.175158","url":null,"abstract":"ABSTRACT Highly conserved DM domain-containing transcription factors (Doublesex/MAB-3/DMRT1) are responsible for generating sexually dimorphic features. In the Drosophila central nervous system, a set of Doublesex (Dsx)-expressing neuroblasts undergo apoptosis in females whereas their male counterparts proliferate and give rise to serotonergic neurons crucial for adult mating behaviour. Our study demonstrates that the female-specific isoform of Dsx collaborates with Hox gene Abdominal-B (Abd-B) to bring about this apoptosis. Biochemical results suggest that proteins AbdB and Dsx interact through their highly conserved homeodomain and DM domain, respectively. This interaction is translated into a cooperative binding of the two proteins on the apoptotic enhancer in the case of females but not in the case of males, resulting in female-specific activation of apoptotic genes. The capacity of AbdB to use the sex-specific isoform of Dsx as a cofactor underlines the possibility that these two classes of protein are capable of cooperating in selection and regulation of target genes in a tissue- and sex-specific manner. We propose that this interaction could be a common theme in generating sexual dimorphism in different tissues across different species. Highlighted Article: Drosophila DoublesexF collaborates with Abdominal-B to generate a sexually dimorphic central nervous system.","PeriodicalId":77105,"journal":{"name":"Development (Cambridge, England). Supplement","volume":"57 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82844670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Katherine Exelby, Edgar Herrera-Delgado, Lorena Garcia Perez, R. Pérez-Carrasco, A. Sagner, Vicki Metzis, Peter Sollich, J. Briscoe
ABSTRACT During development, gene regulatory networks allocate cell fates by partitioning tissues into spatially organised domains of gene expression. How the sharp boundaries that delineate these gene expression patterns arise, despite the stochasticity associated with gene regulation, is poorly understood. We show, in the vertebrate neural tube, using perturbations of coding and regulatory regions, that the structure of the regulatory network contributes to boundary precision. This is achieved, not by reducing noise in individual genes, but by the configuration of the network modulating the ability of stochastic fluctuations to initiate gene expression changes. We use a computational screen to identify network properties that influence boundary precision, revealing two dynamical mechanisms by which small gene circuits attenuate the effect of noise in order to increase patterning precision. These results highlight design principles of gene regulatory networks that produce precise patterns of gene expression. Summary: Experiments and modeling reveal sharp boundaries of gene expression in the vertebrate neural tube depend on the dynamics of the gene regulatory network that patterns the tissue.
{"title":"Precision of tissue patterning is controlled by dynamical properties of gene regulatory networks","authors":"Katherine Exelby, Edgar Herrera-Delgado, Lorena Garcia Perez, R. Pérez-Carrasco, A. Sagner, Vicki Metzis, Peter Sollich, J. Briscoe","doi":"10.1101/721043","DOIUrl":"https://doi.org/10.1101/721043","url":null,"abstract":"ABSTRACT During development, gene regulatory networks allocate cell fates by partitioning tissues into spatially organised domains of gene expression. How the sharp boundaries that delineate these gene expression patterns arise, despite the stochasticity associated with gene regulation, is poorly understood. We show, in the vertebrate neural tube, using perturbations of coding and regulatory regions, that the structure of the regulatory network contributes to boundary precision. This is achieved, not by reducing noise in individual genes, but by the configuration of the network modulating the ability of stochastic fluctuations to initiate gene expression changes. We use a computational screen to identify network properties that influence boundary precision, revealing two dynamical mechanisms by which small gene circuits attenuate the effect of noise in order to increase patterning precision. These results highlight design principles of gene regulatory networks that produce precise patterns of gene expression. Summary: Experiments and modeling reveal sharp boundaries of gene expression in the vertebrate neural tube depend on the dynamics of the gene regulatory network that patterns the tissue.","PeriodicalId":77105,"journal":{"name":"Development (Cambridge, England). Supplement","volume":"49 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81217600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ABSTRACT Sonic hedgehog (Shh), produced in the notochord and floor plate, is necessary for both neural and mesodermal development. To reach the myotome, Shh has to traverse the sclerotome and a reduction of sclerotomal Shh affects myotome differentiation. By investigating loss and gain of Shh function, and floor-plate deletions, we report that sclerotomal Shh is also necessary for neural tube development. Reducing the amount of Shh in the sclerotome using a membrane-tethered hedgehog-interacting protein or Patched1, but not dominant active Patched, decreased the number of Olig2+ motoneuron progenitors and Hb9+ motoneurons without a significant effect on cell survival or proliferation. These effects were a specific and direct consequence of Shh reduction in the mesoderm. In addition, grafting notochords in a basal but not apical location, vis-à-vis the tube, profoundly affected motoneuron development, suggesting that initial ligand presentation occurs at the basal side of epithelia corresponding to the sclerotome-neural tube interface. Collectively, our results reveal that the sclerotome is a potential site of a Shh gradient that coordinates the development of mesodermal and neural progenitors. Summary: Loss- and gain-of-function, and floor plate deletions, reveal that Shh that transits through the sclerotome is presented to the neuroepithelium from its basal aspect to affect motoneuron development.
{"title":"Neural tube development depends on notochord-derived sonic hedgehog released into the sclerotome","authors":"N. Kahane, Chaya Kalcheim","doi":"10.1101/639831","DOIUrl":"https://doi.org/10.1101/639831","url":null,"abstract":"ABSTRACT Sonic hedgehog (Shh), produced in the notochord and floor plate, is necessary for both neural and mesodermal development. To reach the myotome, Shh has to traverse the sclerotome and a reduction of sclerotomal Shh affects myotome differentiation. By investigating loss and gain of Shh function, and floor-plate deletions, we report that sclerotomal Shh is also necessary for neural tube development. Reducing the amount of Shh in the sclerotome using a membrane-tethered hedgehog-interacting protein or Patched1, but not dominant active Patched, decreased the number of Olig2+ motoneuron progenitors and Hb9+ motoneurons without a significant effect on cell survival or proliferation. These effects were a specific and direct consequence of Shh reduction in the mesoderm. In addition, grafting notochords in a basal but not apical location, vis-à-vis the tube, profoundly affected motoneuron development, suggesting that initial ligand presentation occurs at the basal side of epithelia corresponding to the sclerotome-neural tube interface. Collectively, our results reveal that the sclerotome is a potential site of a Shh gradient that coordinates the development of mesodermal and neural progenitors. Summary: Loss- and gain-of-function, and floor plate deletions, reveal that Shh that transits through the sclerotome is presented to the neuroepithelium from its basal aspect to affect motoneuron development.","PeriodicalId":77105,"journal":{"name":"Development (Cambridge, England). Supplement","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80482679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Regeneration is an adult developmental process considered to be an epiphenomenon of embryonic development. Although several studies have shown that various embryonic genes are expressed during regeneration, there have been no large-scale, direct and functional comparative studies between the development and regeneration of a specific structure in one animal. Here, we use the brittle star Amphiura filiformis to characterise the role of the FGF signalling pathway during skeletal development and regeneration. In both processes, we find the ligands expressed in ectodermal cells flanking underlying mesodermal cells, and the receptors expressed specifically by these skeletogenic cells. Perturbation of FGF but not VEGF signalling during skeletogenesis completely inhibited skeleton formation in both embryogenesis and regeneration, without affecting other key developmental processes like cell migration or proliferation. Transcriptome-wide differential analysis identified a highly similar cohort of skeletogenic differentiation genes downstream of the FGF signalling pathway, whereas upstream transcription factors involved in the initial specification of the skeletogenic lineage where unaffected. Comparison to the sea urchin indicated that many of the affected genes are associated with differentiation. Moreover, several genes showed no homology to a cohort from other species, leading to the discovery of brittle star specific, downstream skeletogenic genes. In conclusion, our results show that the FGF pathway is crucial for skeletogenesis in the brittle star, as it is in other deuterostomes, and for the first time provide evidence for the re-deployment of a gene regulatory module during both regeneration and development.
{"title":"FGF signalling plays similar roles in development and regeneration of the skeleton in the brittle star Amphiura filiformis","authors":"A. Czarkwiani, D. Dylus, L. Carballo, P. Oliveri","doi":"10.1101/632968","DOIUrl":"https://doi.org/10.1101/632968","url":null,"abstract":"Regeneration is an adult developmental process considered to be an epiphenomenon of embryonic development. Although several studies have shown that various embryonic genes are expressed during regeneration, there have been no large-scale, direct and functional comparative studies between the development and regeneration of a specific structure in one animal. Here, we use the brittle star Amphiura filiformis to characterise the role of the FGF signalling pathway during skeletal development and regeneration. In both processes, we find the ligands expressed in ectodermal cells flanking underlying mesodermal cells, and the receptors expressed specifically by these skeletogenic cells. Perturbation of FGF but not VEGF signalling during skeletogenesis completely inhibited skeleton formation in both embryogenesis and regeneration, without affecting other key developmental processes like cell migration or proliferation. Transcriptome-wide differential analysis identified a highly similar cohort of skeletogenic differentiation genes downstream of the FGF signalling pathway, whereas upstream transcription factors involved in the initial specification of the skeletogenic lineage where unaffected. Comparison to the sea urchin indicated that many of the affected genes are associated with differentiation. Moreover, several genes showed no homology to a cohort from other species, leading to the discovery of brittle star specific, downstream skeletogenic genes. In conclusion, our results show that the FGF pathway is crucial for skeletogenesis in the brittle star, as it is in other deuterostomes, and for the first time provide evidence for the re-deployment of a gene regulatory module during both regeneration and development.","PeriodicalId":77105,"journal":{"name":"Development (Cambridge, England). Supplement","volume":"59 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80886699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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