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 precursors were transfected in vivo with c-src, n-src, or constitutively active mutants. Axonogenesis of retinal ganglion cells was markedly impaired by the expression of constitutively active c-src and only mildly affected by the expression of constitutively active n-src. This differential phenotype could not be accounted for by raised levels of intracellular tyrosine phosphorylation alone because the average anti-phosphotyrosine staining intensity of retinal neurons expressing mutant n-src 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 overlapping and distinct activities in differentiating retinal neurons.
Worley
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Department of Biology 0366, University of California, San Diego, La Jolla 92093, USA.
Cornel
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Holt
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D000818:Animals; D001369:Axons / Q000502:physiology*; D002454:Cell Differentiation; D002645:Chickens / Q000235:genetics; D004274:DNA, Recombinant; D004625:Embryo, Nonmammalian / Q000502:physiology; D005314:Embryonic and Fetal Development; D005260:Female; D015870:Gene Expression; D016391:Genes, src; D007536:Isomerism; D009434:Neural Pathways / Q000196:embryology; D010766:Phosphorylation; D010786:Photoreceptor Cells / Q000166:cytology; D010860:Pigments, Biological / Q000378:metabolism; D012160:Retina / Q000196:embryology*; D012165:Retinal Ganglion Cells / Q000502:physiology; D014443:Tyrosine / Q000378:metabolism; D014982:Xenopus laevis
D004274:DNA, Recombinant; D010860:Pigments, Biological; D014443:Tyrosine