VESSEL PATTERNING IN THE EMBRYO OF THE ZEBRAFISH - GUIDANCE BY NOTOCHORD

We have cloned the zebrafish homolog of the receptor tyrosine kinase f lk-1 to provide us with a tool to study normal vascular pattern format ion in the developing zebrafish embryo and to compare it to mutants in which vascular pattern is perturbed. We find that during normal devel opment the first angioblasts arise laterally in the mesoderm and then migrate medially to form the primordia of the large axial vessels, the dorsal aorta (axial artery) and the axial vein. Lumen formation occur s shortly before onset of circulation at 24 hr postfertilization. We e xamined the specification of vascular progenitors in the mutant cloche , which fails to form both vessels and blood. cloche lacks all flk-exp ressing cells and therefore appears to lack angioblasts. The axial ves sels of the trunk form in close proximity to notochord and endoderm, w hich may provide cues for their formation. The dorsal aorta is normall y just ventral to the notochord; the axial vein is just below the dors al aorta and above the endoderm. floating head (flh) and no tail (ntl) mutants both have defects in the formation of notochord. Both are cel l-autonomous lesions, flh abolishing notochord and ntl preventing its differentiation. In both mutants the dorsal aorta fails to form, while formation of the axial vein is less affected. Mosaic analysis of muta nt embryos shows that transplanted wild-type cells can become notochor d in mutant flh embryos. In these mosaic embryos flh cells expressing flk assemble at the midline, beneath the wild-type notochord, and form an aortic primordium. This suggests that signals from the notochord m ay guide angioblasts in the fashiong of the dorsal aorta. The notochor d seems to be less important for the formation of the vein. (C) 1997 A cademic Press.