GRIDLOCK, A LOCALIZED HERITABLE VASCULAR PATTERNING DEFECT IN THE ZEBRAFISH

We are using the zebrafish, Danio rerio, to identify genes that genera te and pattern the vertebrate vasculature. We have isolated a recessiv e mutation, gridlock(m145) (grl(m145)) in which blood flow to the tail is impeded by a localized vascular defect. Using a novel microangiogr aphic method, we show that the blockade is in the anterior trunk, wher e the paired lateral dorsal aortae normally merge to form the single m idline aorta. Arterial-venous shunts and collateral vessels develop in most mutant embryos, bypassing the lesion and reconstituting caudal b lood flow. The grl defect resembles coarctation of the aorta, a human congenital cardiovascular malformation of unknown aetiology, in the lo cation of the lesion and its consequences and in the mutants' dependen ce on collateral vessels for survival.