Dlc1controls cardio-vascular development downstream of Vegfa/Kdrl/Nrp1 signaling in the zebrafish embryo

Abstract

ABSTRACTThe family ofdeleted-in-liver-cancer (dlc)genes encodes RhoGTPases and plays pivotal roles in cardiovascular development, but animal models for studying their functions are sparse due to early embryonic lethality. Gain and loss of function ofdlc1anddlc3severely altered the growth of intersegmental vessels in the trunk of zebrafish embryos. Additionally, overexpression ofdlc1affected the growth of the common cardinal veins, but could rescue the arrest of angiogenesis induced by Vegfr2 inhibition, placingdlc1downstream ofkdrlsignaling. Loss ofdlc1negatively affected the lumenization of the first aortic arch arteries and the lateral dorsal aortae.dlc1mutants displayed a full obstruction in the early outflow tract during cardiac morphogenesis, which models to alterations in DLC1 detected in congenital heart defects in human patients. This study provides a functionalin vivocharacterization ofdlc1anddlc3during vertebrate embryogenesis and placesdlc1as a key gene to control vascular development.