Open AccessGenome-wide strategies reveal target genes of Npas4l associated with vascular development in zebrafish
Author(s) -
Michele Marass,
Arica Beisaw,
Claudia Gerri,
Francesca Luzzani,
Naoto Fukuda,
Stefan Günther,
Carsten Kuenne,
Sven Reischauer,
Didier Y.R. Stainier
Publication year - 2019
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.754
H-Index - 325
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.173427
Subject(s) - biology , zebrafish , transcription factor , transcriptome , chromatin immunoprecipitation , crispr , gene , computational biology , regulator , genetics , genome , enhancer , function (biology) , chromatin , gene expression , promoter
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.