OVEREXPRESSION OF C-SRC AND N-SRC IN THE DEVELOPING XENOPUS RETINA DIFFERENTIALLY IMPAIRS AXONOGENESIS

To compare the roles of the nonreceptor tyrosine kinase c-src and its neuronal splice form n-src in developing neurons, Xenopus retinal prec ursors were transfected in vivo with c-src, n-src, or constitutively a ctive mutants. Axonogenesis of retinal ganglion cells was markedly imp aired by the expression of constitutively active c-src and only mildly affected by the expression of constitutively active n-src. This diffe rential phenotype could not be accounted for by raised levels of intra cellular tyrosine phosphorylation alone because the average anti-phosp hotyrosine staining intensify of retinal neurons expressing mutant n-s rc was almost twofold greater than that of neurons expressing mutant c -src. The expression of either constitutively active isoform inhibited photoreceptor differentiation by 72% but did not influence other cell fates. These results suggest that c-src and n-src have both overlappi ng and distinct activities in differentiating retinal neurons.