P59(FYN) AND PP60C-(SRC) MODULATE AXONAL GUIDANCE IN THE DEVELOPING MOUSE OLFACTORY PATHWAY

The Src-family tyrosine kinases p59(fyn) and pp60(c-src) are localized on axons of the mouse olfactory nerve during the initial stages of ax onal growth, but their functional roles remain to be defined. To study the role of these kinases, we analyzed the trajectory of the olfactor y nerve in E11.5 homozygous null mutant mice lacking single src or fyn genes and double mutants lacking both genes. Primary olfactory axons of single and double mutants exited the olfactory epithelium and proje cted toward the telencephalon, but displayed differences in fasciculat ion, The fyn-minus olfactory nerve had significantly more fascicles th an the src-minus nerve. Most strikingly, the primary olfactory nerve o f src/fyn double mutants showed the greatest degree of defasciculation , These defects, identified by NCAM labeling, were not due to apparent changes in the size of the olfactory epithelium, With the exception o f the src-minus mice, which had fewer fascicles than the wild type, no obvious differences were observed in coalescence of vomeronasal axons from mutant mice. The mesenchyme of the double and single mutants exh ibited only subtle changes in laminin and fibronectin staining, indica ting that the adhesive environment of the mesenchyme may contribute in part to defects in fasciculation, The results suggest that signaling pathways mediated by p59(fyn) and pp60(c-src) contribute to the approp riate fasciculation of axons in the nascent olfactory system, and comp rise partially compensatory mechanisms for axonal adhesion and guidanc e. (C) 1998 John Wiley & Sons, Inc.