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ZFIN ID: ZDB-PUB-190518-4
Genome-wide strategies reveal target genes of Npas4l associated with vascular development in zebrafish
Marass, M., Beisaw, A., Gerri, C., Luzzani, F., Fukuda, N., Günther, S., Kuenne, C., Reischauer, S., Stainier, D.Y.R.
Date: 2019
Source: Development (Cambridge, England)   146(11): (Journal)
Registered Authors: Reischauer, Sven, Stainier, Didier
Keywords: ATAC-seq, Angioblast, ChIP-seq, Cloche, Endothelial cell differentiation, Npas4l
Microarrays: GEO:GSE130196, GEO:GSE130198, GEO:GSE130199, GEO:GSE130200, GEO:GSE130202
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Basic Helix-Loop-Helix Transcription Factors/metabolism
  • Basic Helix-Loop-Helix Transcription Factors/physiology*
  • Binding Sites/genetics
  • Cell Differentiation/genetics
  • Chromosome Mapping/methods
  • Datasets as Topic
  • Embryo, Nonmammalian
  • Endothelial Cells/physiology
  • Endothelium, Vascular/embryology*
  • Endothelium, Vascular/metabolism
  • Gene Expression Regulation, Developmental*
  • Genomics/methods
  • LIM Domain Proteins/genetics
  • Neovascularization, Physiologic/genetics*
  • T-Cell Acute Lymphocytic Leukemia Protein 1/genetics
  • Transcription Factors/genetics
  • Zebrafish*/embryology
  • Zebrafish*/genetics
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Zebrafish Proteins/physiology*
PubMed: 31097478 Full text @ Development
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 remains incomplete. Zebrafish cloche/npas4l mutants have been used broadly as an avascular model, but little is known about the molecular mechanisms of action of the Npas4l transcription factor. Here, to identify its direct and indirect target genes, we combined complementary genome-wide approaches including transcriptome analyses and chromatin immunoprecipitation. The cross-analysis of these datasets indicates that Npas4l functions as a master regulator by directly inducing a group of transcription factor genes crucial for hematoendothelial specification such as etv2, tal1 and lmo2 We also identified new targets of Npas4l and investigated the function of a subset of them using the CRISPR/Cas9 technology. Phenotypic characterization of tspan18b mutants reveals a novel player in developmental angiogenesis, confirming the reliability of the datasets generated. Collectively, these data represent a useful resource for future studies aimed to better understand EC fate determination and vascular development.