A genetic screen for vascular mutants in zebrafish reveals dynamic roles for Vegf/Plcg1 signaling during artery development

摘要: Abstract In this work we describe a forward genetic approach to identify mutations that affect blood vessel development in the zebrafish. By applying haploid screening strategy transgenic background allows direct visualization of vessels, it was possible several classes mutant vascular phenotypes. Subsequent characterization lines revealed defects Vascular endothelial growth factor (Vegf) signaling specifically affected artery development. Comparison phenotypes associated with different within functional zebrafish Vegf receptor-2 ortholog (referred as kdr-like, kdrl) surprisingly varied effects on parallel, identified an allelic series phospholipase c gamma 1 (plcg1). Together vivo structure–function analysis, our results suggest requirement for Plcg1 catalytic activity downstream receptor tyrosine kinases. We further find embryos lacking both maternal and zygotic plcg1 display more severe differentiation but are otherwise similar mutants. Finally, demonstrate through mosaic analysis functions autonomously cells. analyses Vegf/Plcg1 acts at multiple time points contexts mediate distinct aspects