Endocardial identity is established during early somitogenesis by Bmp signalling acting upstream of npas4l and etv2
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PROVIDER: PRJNA832312 | ENA |
REPOSITORIES: ENA
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Project description:The endocardium plays important roles in the development and function of the vertebrate heart; however, few molecular markers of this tissue have been identified and little is known about what regulates its differentiation. Here, we describe the Gt(SAGFF27C); Tg(4xUAS:egfp) line as a marker of endocardial development in zebrafish. Transcriptomic comparison between endocardium and pan-endothelium confirms molecular distinction between these populations and time-course analysis suggests differentiation as early as eight somites. To investigate what regulates endocardial identity, we employed npas4l, etv2 and scl loss-of-function models. Endocardial expression is lost in npas4l mutants, significantly reduced in etv2 mutants and only modestly affected upon scl loss-of-function. Bmp signalling was also examined: overactivation of Bmp signalling increased endocardial expression, whereas Bmp inhibition decreased expression. Finally, epistasis experiments showed that overactivation of Bmp signalling was incapable of restoring endocardial expression in etv2 mutants. By contrast, overexpression of either npas4l or etv2 was sufficient to rescue endocardial expression upon Bmp inhibition. Together, these results describe the differentiation of the endocardium, distinct from vasculature, and place npas4l and etv2 downstream of Bmp signalling in regulating its differentiation.
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Project description:The development of a vascular network is essential to nourish tissues and sustain organ function throughout life. Endothelial cells (ECs) are the building blocks of blood vessels, yet our understanding of EC specification in vertebrates remains incomplete. cloche/npas4l mutants have broadly been used as an avascular model in zebrafish, but little is known about the molecular mechanism of action of Npas4l. Here, to identify the direct and indirect target genes of this transcription factor, we combined complementary genome-wide approaches, including transcriptome analyses and chromatin immunoprecipitation (ChIP). The cross-analysis of these datasets indicate that Npas4l functions as a master regulator by directly inducing a wave of transcription factor genes crucial for hematoendothelial specification in vertebrates, including etv2, tal1, and lmo2. We identified additional target genes acting downstream of npas4l and investigated the function of a subset of them using CRISPR/Cas9 technology. Phenotypic characterization of tspan18b mutants reveals a novel role for tspan18b in developmental angiogenesis, confirming the reliability of the datasets generated. Collectively, these data represent a useful resource for future studies aimed to investigate novel genes with a potential role in vascular development and EC fate determination in vertebrates.
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Project description:The development of a vascular network is essential to nourish tissues and sustain organ function throughout life. Endothelial cells (ECs) are the building blocks of blood vessels, yet our understanding of EC specification in vertebrates remains incomplete. cloche/npas4l mutants have broadly been used as an avascular model in zebrafish, but little is known about the molecular mechanism of action of Npas4l. Here, to identify the direct and indirect target genes of this transcription factor, we combined complementary genome-wide approaches, including transcriptome analyses and chromatin immunoprecipitation (ChIP). The cross-analysis of these datasets indicate that Npas4l functions as a master regulator by directly inducing a wave of transcription factor genes crucial for hematoendothelial specification in vertebrates, including etv2, tal1, and lmo2. We identified additional target genes acting downstream of npas4l and investigated the function of a subset of them using CRISPR/Cas9 technology. Phenotypic characterization of tspan18b mutants reveals a novel role for tspan18b in developmental angiogenesis, confirming the reliability of the datasets generated. Collectively, these data represent a useful resource for future studies aimed to investigate novel genes with a potential role in vascular development and EC fate determination in vertebrates.
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Project description:The development of a vascular network is essential to nourish tissues and sustain organ function throughout life. Endothelial cells (ECs) are the building blocks of blood vessels, yet our understanding of EC specification in vertebrates remains incomplete. cloche/npas4l mutants have broadly been used as an avascular model in zebrafish, but little is known about the molecular mechanism of action of Npas4l. Here, to identify the direct and indirect target genes of this transcription factor, we combined complementary genome-wide approaches, including transcriptome analyses and chromatin immunoprecipitation (ChIP). The cross-analysis of these datasets indicate that Npas4l functions as a master regulator by directly inducing a wave of transcription factor genes crucial for hematoendothelial specification in vertebrates, including etv2, tal1, and lmo2. We identified additional target genes acting downstream of npas4l and investigated the function of a subset of them using CRISPR/Cas9 technology. Phenotypic characterization of tspan18b mutants reveals a novel role for tspan18b in developmental angiogenesis, confirming the reliability of the datasets generated. Collectively, these data represent a useful resource for future studies aimed to investigate novel genes with a potential role in vascular development and EC fate determination in vertebrates.
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Project description:Screening for genes up in Etv2+ cells within Flk-1+ ES derived mesoderm Microarray analysis performed to screen for the candidate genes regulated by Etv2. Differentiated Flk-1+ mesoderm can be devided into Etv2+ or-. Etv2+ cells are assumed to be committed to hemato/endothelial cells. Comparison of two populations can reveal genes relevant in this commitment. Extract RNA from sorted Flk-1+/Etv2- vs Flk-1+/Etv2+ populations.Etv2-Venus KI ES cells were differentiated on OP9 for 4-5 days and Flk-1+ population was separated into Etv2-Venus+ or- cells. Total RNA was purified from each population for analysis.
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