FLK-1, A RECEPTOR FOR VASCULAR ENDOTHELIAL GROWTH-FACTOR (VEGF), IS EXPRESSED BY RETINAL PROGENITOR CELLS

Throughout development of the vertebrate retina, progenitor cells are multipotential, producing a variety of distinctive cell types. Little is known of the molecular mechanisms directing the determination of ce ll fate. We have examined retinal progenitor cells for expression of r eceptor tyrosine kinases in an attempt to define receptors that could allow a progenitor to respond to its environment. We found that the re ceptor tyrosine kinase Flk-1, previously shown to be expressed in endo thelial cells, is also expressed in neural progenitor cells of the mou se retina. Flk-1 RNA expression in the retinal progenitors commences w ith the onset of neuronal differentiation and persists throughout reti nal neurogenesis. Flk-1 RNA and protein levels in the retina vary temp orally during development, as shown by in situ hybridization and Weste rn blot analysis. Patterns of beta-galactosidase expression in mice co ntaining the lacZ gene in place of the Flk-1 gene are consistent with Flk-1 being expressed in retinal progenitors. In addition, we show tha t the ligand of Flk-1, vascular endothelial growth factor (VEGF), is e xpressed in the developing retina by differentiated cells and that a c himeric ligand of VEGF fused to alkaline phosphatase binds to prolifer ating retinal progenitors. Furthermore, the neural retina-derived Flk- 1 protein kinase is activated by VEGF in vitro. Thus, the Flk-1 recept or protein kinase is expressed on the surface of neural progenitors in mouse retina and may play a critical role in neurogenesis as well as in vasculogenesis.