Concomitant expression of genes encoding integrin alpha v beta 5 heterodimer and vitronectin in growing parallel fibers of postnatal rat cerebellum: a possible role as mediators of parallel fiber elongation.

External granule cells in the premigratory zone and the upper molecular layer of neonatal rat cerebellum elongate their neurites (parallel fibers) bidirectionally before and during migration into the internal granular layer. In the present study, it is shown that integrin alpha v beta 5 heterodimer (INT alpha v beta 5) is expressed in parallel fibers in these layers at postnatal days 3-20, but not in migrating granule cells or mature parallel fibers. Vitronectin (VN), the dominant ligand for INT alpha v beta 5, was concomitantly detected in the premigratory zone and the upper molecular layer during this period. Several other subunits including alpha 1-6 and beta 1-4 were not detected. When granule cells were prepared from postnatal cerebella and cultured for a few days, the parallel fibers elongated well in response to VN, but the granule cells did not migrate on VN. This fiber elongation was specifically inhibited by both anti-INT alpha v beta 5 antibody and peptides containing Arg-Gly-Asp (RGD), a sequence responsible for cell adhesion mediated by VN. Neither control integrin antibody against integrin alpha v beta 3 heterodimer nor control peptides containing Arg-Gly-Glu (RGE) showed an inhibitory effect on fiber elongation. These observations strongly suggest that the INT alpha v beta 5 VN receptor plays a role in the elongation of parallel fibers from granule cells during cerebellar histogenesis, but its expression is not required for their maintenance or granule cell migration. INT alpha v beta k could be considered as a new marker of parallel fibers during cerebellar development.