RT Journal Article
SR Electronic
T1 Genome-wide strategies reveal target genes of Npas4l associated with cardiovascular development in zebrafish
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 461988
DO 10.1101/461988
A1 Marass, Michele
A1 Beisaw, Arica
A1 Gerri, Claudia
A1 Luzzani, Francesca
A1 Fukuda, Nana
A1 Günther, Stefan
A1 Kuenne, Carsten
A1 Reischauer, Sven
A1 Stainier, Didier Y. R.
YR 2018
UL http://biorxiv.org/content/early/2018/11/04/461988.abstract
AB 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 (ChIP). 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.