IMPAIRED NEURITE OUTGROWTH OF SRC-MINUS CEREBELLAR NEURONS ON THE CELL-ADHESION MOLECULE L1

The nonreceptor tyrosine protein kinases pp60(c-src), p59(fyn), and pp62(c-yes) are localized in growth cones of developing neurons, but their function is undefined. To determine whether these tyrosine kinases were capable of regulating substrate-dependent axon growth, cultures of cerebellar neurons from wild-type, src(-), fyn(-), and yes(-) mice were analyzed for neurite outgrowth on the neural cell adhesion molecule L1 or the extracellular matrix protein laminin. The rate of neurite extension on L1 was reduced in src(-), but not in fyn(-) or yes(-) neurons. Neurite extension on laminin was unaltered in src(-), fyn(-), or yes(-) neurons, indicating that pp60(c-src), p59(fyn), or pp62(c-yes) is not likely to participate in integrin-dependent axon growth. These results demonstrate that pp60(c-src) is a component of the intracellular signaling pathway in L1-mediated axonal growth and suggest that Src-related nonreceptor tyrosine kinases may have distinct, nonredundant functions in the nervous system.