MANY MAJOR CNS AXON PROJECTIONS DEVELOP NORMALLY IN THE ABSENCE OF SEMAPHORIN-III

The semaphorins constitute a large gene family of transmembrane and se creted molecules, many of which are expressed in the nervous system. G enetic studies in Drosophila have revealed a role for semaphorins in a xon guidance and synapse formation, and several in vitro studies in mi ce have demonstrated a dramatic chemorepellent effect of semaphorin II I (Sema III) on the axons of several populations of neurons. To invest igate the function of Sema III during in vivo axon guidance in the mam malian CNS, we studied the development of axonal projections in mutant mice lacking Sema ill. Projections were studied for which either the in vitro evidence suggests a role for Sema III in axon guidance (e.g., cerebellar mossy fibers, thalamocortical axons, or cranial motor neur ons) or the in vivo expression suggests a role for Sema III in axon gu idance (e.g., cerebellar Purkinje cells, neocortex). We find that many major axonal projections, including climbing fiber, mossy fiber, thal amocortical, and basal forebrain projections and cranial nerves, devel op normally in the absence of Sema ill. Despite its in vitro function and in vivo expression, it appears as if Sema III is not absolutely re quired for the formation of many major CNS tracts. Such data are consi stent with recent models suggesting that axon guidance is controlled b y a balance of forces resulting from multiple guidance cues. Our data lead us to suggest that if Sema III functions in part to guide the for mation of major axonal projections, then it does so in combination wit h both other semaphorins and other families of guidance molecules. (C) 1998 Academic Press.