NCAM-DEPENDENT NEURITE OUTGROWTH IS INHIBITED IN NEURONS FROM FYN-MINUS MICE

Src-related nonreceptor protein tyrosine kinases in nerve growth cones (p59(fyn), pp60(c-src), and pp62(c-yes)) potential intracellular sign aling molecules for cell adhesion molecule-directed axonal growth. To determine whether src-related tyrosine kinases mediate NCAM-dependent neurite outgrowth, cultures of cerebellar and sensory neurons from fyn (-), src(-), and yes(-) minus mice were analyzed for neurite outgrowth on monolayers of NCAM140-transfected L fibroblasts. NCAM-dependent ne urite outgrowth was selectively inhibited in cultures of cerebellar an d dorsal root ganglion neurons from fyn(-), but not src(-) or yes(-) m ice. Neurite outgrowth by fyn(-), src(-), or yes(-) neurons on untrans fected fibroblast monolayers was unaffected, indicating that these kin ases do not contribute significantly to axon growth on at least some i ntegrins or other adhesive substrates present on fibroblasts. This stu dy demonstrates that p59(fyn) is an essential component of the NCAM si gnaling pathway leading to axonal growth.