NEURONAL PATHFINDING IS ABNORMAL IN MICE LACKING THE NEURONAL GROWTH CONE PROTEIN GAP-43

GAP-43 has been termed a ''growth'' or ''plasticity'' protein because it is expressed at high levels in neuronal growth cones during develop ment and during axonal regeneration. By homologous recombination, we g enerated mice lacking GAP-43. The mice die in the early postnatal peri od. GAP-43-deficient retinal axons remain trapped in the chiasm for 6 days, unable to navigate past this midline decision point. Over the su bsequent weeks of life, most GAP-43-deficient axons do enter the appro priate tracts, and the adult CNS is grossly normal. There is no eviden ce for interference with nerve growth rate, and cultured neurons exten d neurites and growth cones in a fashion indistinguishable from contro ls. Thus, the GAP-43 protein is not essential for axonal outgrowth or growth cone formation pet se, but is required at certain decision poin ts, such as the optic chiasm. This is compatible with the hypothesis t hat GAP-43 serves to amplify pathfinding signals from the growth cone.