Induction of presynaptic differentiation in cultured neurons by extracellular matrix components

Motoneurons reinnervating skeletal muscles form nerve terminals at sites of contact with a specialized basal lamina. To analyse the molecules and mechanisms that underly these responses, we introduce two systems in which basal lamina-derived components induce presynaptic differentiation of cultured neurons from chick ciliary ganglia in the absence of a postsynaptic cell. In one, ciliary neurites that contact substrates coated with a recombinant laminin beta2 fragment form varicosities that are rich in synaptic vesicle proteins, depleted of neurofilaments, and capable of depolarization-dependent exocytosis and endocytosis. Thus, a single molecule can trigger a complex, coordinated program of presynaptic differentiation. In a second system, neurites growing on cryostat sections of adult kidney form vesicle-rich, neurofilament-poor arbors on glomeruli. Glomerular basal lamina, like synaptic basal lamina, is rich in laminin beta2 and collagen (alpha3-5) IV. However, glomeruli from mutant mice lacking these proteins were capable of inducing differentiation, suggesting the glomerulus as a source of novel presynaptic organizing molecules.