Impaired neurite outgrowth of src-minus cerebellar neurons on the cell adhesion molecule L1

The nonreceptor tyrosine protein kinases pp60^c-src, p590^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 fyb^- 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, non-redundant functions in the nervous system.