Distribution of GAP-43 mRNA 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 nucleus was examined at birth, during postnatal development and in the adult by both Northern and in situ hybridization. Northern blot analysis revealed that cerebellar GAP-43 mRNA expression increases from birth 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 cerebellar nuclei and the inferior olive were also intensely labeled at birth. GAP-43 mRNA was localized in granule cells during their migration through the molecular layer of the developing cerebellum and after their arrival in the internal granule cell layer. By PD 21, the pattern 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 and none in the molecular layer. Purkinje cells were devoid of GAP-43 mRNA throughout the postnatal and adult periods. In light of our observations, we propose that GAP-43 is a critical factor in granule cell differentiation/migration, as well as in parallel and climbing fiber axonal outgrowth and synaptogenesis during development. Localization of GAP-43 mRNA within granule and inferior olivary cells of adult animals indicates that GAP-43 protein observed in the molecular layer is transported from these cells to their terminals in the molecular layer suggesting that GAP-43 is also an intrinsic presynaptic determinant in cerebellar neuroplasticity.