DISTRIBUTION OF GAP-43 MESSENGER-RNA IN THE IMMATURE AND ADULT CEREBELLUM - A ROLE FOR GAP-43 IN CEREBELLAR DEVELOPMENT AND NEUROPLASTICITY

Expression of GAP-43 mRNA in the rat cerebellum and inferior olivary n ucleus was examined at birth, during postnatal development and in the adult by both Northern and in situ hybridization. Northern blot analys is revealed that cerebellar GAP-43 mRNA expression increases from birt h to postnatal day (PD) 7 and then declines to a lower level the adult . At birth, in situ hybridization experiments showed intense labeling of GAP-43 mRNA in the premigratory, but not the germinal, zone of the cerebellar external granule cell layer. Localization of GAP-43 within the premigratory zone, a layer containing post-mitotic granule cells, indicates that granule cells begin expressing GAP-43 mRNA after final mitosis and during axonal outgrowth of the parallel fibers. The deep c erebellar nuclei and the inferior olive were also intensely labeled at birth. GAP-43 mRNA was localized in granule cells during their migrat ion through the molecular layer of the developing cerebellum and after their arrival in the internal granule cell layer. By PD 21, the patte rn of GAP-43 expression was similar to that observed in the adult; GAP -43 mRNA was localized to the internal granule layer and the inferior olive with minimal to no hybridization in the deep cerebellar nuclei a nd none in the molecular layer. Purkinje cells were devoid of GAP-43 m RNA throughout the postnatal and adult periods. In light of our observ ations, we propose that GAP-43 is a critical factor in granule cell di fferentiation/migration, as well as in parallel and climbing fiber axo nal outgrowth and synaptogenesis during development. Localization of G AP-43 mRNA within granule and inferior olivary cells of adult animals indicates that GAP-43 protein observed in the molecular layer is trans ported from these cells to their terminals in the molecular layer sugg esting that GAP-43 is also an intrinsic presynaptic determinant in cer ebellar neuroplasticity.