Laminin-like proteins are differentially regulated during cerebellar development and stimulate granule cell neurite outgrowth in vitro.

The basement membrane glycoprotein laminin-1 is a potent stimulator of neurite outgrowth. Although a variety of laminin isoforms have been described in recent years, the role of alternative laminin isoforms in neural development remains largely uncharacterized. We found that a polyclonal antibody raised against the alpha1, beta1, and gamma1 chains of laminin-1 and a monoclonal antibody raised against the alpha2 chain of laminin-2 detect immunoreactive material in neuronal cell bodies in the developing mouse cerebellum. In addition, laminin-1-like immunoreactivity was found in cell types throughout the cerebellum, but laminin-alpha2-like immunoreactivity was restricted to the Purkinje cells. Purified laminin-1 and laminin-2 stimulated neurite outgrowth in primary cultures of mouse cerebellar granule neurons to a similar extent, whereas the synthetic peptides tested appeared to be active only for cell adhesion and not for stimulation of neurite outgrowth. The E8 proteolytic fragment of laminin-1 contained full neurite outgrowth activity. The identity of laminins expressed in granule neurons was also examined by Western blotting; laminin-like complexes were associated with the cell and appeared to have novel compositions. These results suggest that laminin-like complexes play important roles in cerebellar development.