Induction of presynaptic differentiation in cultured neurons by extracellular matrix components


: Professor J. R. Sanes, as above.


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 β2 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 β2 and collagen (α3–5) 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.