Ocular vessel patterning in zebrafish is indirectly regulated by Hedgehog signaling

The superficial ocular vasculature of the embryonic zebrafish develops in a highly stereotypic manner and hence provides a convenient model for studying molecular mechanisms that regulate vascular patterning. We have used transgenic zebrafish embryos in which all endothelial cells express enhanced Green Fluorescent Protein and small molecule inhibitors to examine the contribution of two signaling pathways, vascular endothelial growth factor (VEGF) and Hedgehog (Hh) pathways, to the development of the superficial system. We find that most, but not all vessels of the superficial system depend on VEGF signaling for their growth. Hh signaling appears to limit superficial vessel growth over the dorsal eye and is required to promote superficial vessel growth over the ventral eye. These effects of Hh signaling are indirect. Our initial analyses of factors that regulate growth and patterning of superficial ocular vessels suggest that early patterning events in the embryo during organogenesis stages could influence vascular patterning later on. By studying development of specific vascular systems it should be possible to identify new roles for signaling pathways in regulating vascular development.