A role for the Fibroblast Growth Factor Receptor in cell fate decisions inthe developing vertebrate retina

The mature vertebrate retina contains seven major cell types that develop f rom an apparently homogenous population of precursor cells, Clonal analyses have suggested that environmental influences play a major role in specifyi ng retinal cell identity, Fibroblast growth factor-2 is present in the deve loping retina and regulates the survival, proliferation and differentiation of developing retinal cells in culture. Here we have tested whether fibrob last growth factor receptor signaling biases retinal cell fate decisions in vivo. Fibroblast growth factor receptors were inhibited in retinal precurs ors in Xenopus embryos by expressing a dominant negative form of the recept or, XFD, Dorsal animal blastomeres that give rise to the retina were inject ed with cDNA expression constructs for XFD and a control non-functional mut ant receptor, D48, and the cell fates of transgene-expressing cells in the mature retina determined. Fibroblast growth factor receptor blockade result s in almost a 50% loss of photoreceptors and amacrine cells, and a concurre nt 3.5-fold increase in Muller glia, suggesting a shift towards a Muller ce ll fate in the absence of a fibroblast growth factor receptor signal, Inhib ition of non-fibroblast-growth-factor-mediated receptor signaling with a th ird mutant receptor, HAVO alters cell fate in an opposite manner. These res ults suggest that it is the balance of fibroblast growth factor and non-fib roblast growth factor ligand signals that influences retinal cell genesis.