ABERRANT DIFFERENTIATION OF NEUROMUSCULAR-JUNCTIONS IN MICE LACKING S-LAMININ LAMININ BETA-2

SYNAPSE formation requires a complex interchange of information betwee n the pre- and postsynaptic partners. At the skeletal neuromuscular ju nction, some of this information is contained in the basal lamina (BL) , which runs through the synaptic cleft between the motor nerve termin al and the muscle fibre. During regeneration following injury, compone nts of synaptic BL can trigger several features of postsynaptic differ entiation in the absence of the nerve terminal, and of presynaptic dif ferentiation in the absence of the muscle fibre(1-3). One nerve-derive d component of synaptic BL, agrin, is known to affect postsynaptic dif ferentiation3, but no muscle-derived components have yet been shown to influence motor nerve terminals. A candidate for such a role is s-lam inin (also called laminin beta 2), a homologue of the B1 (beta 1) chai n of the widely distributed BL glycoprotein, laminin(30). s-laminin is synthesized by muscle cells(5) and concentrated in synaptic BL(4). In vitro, recombinant s-laminin fragments are selectively adhesive for m otor neuron-like cells, inhibit neurite outgrowth promoted by other ma trix molecules, and act as a 'stop signal' for growing neurites(6,7). By generating and characterizing mice with a targeted mutation of the s-laminin gene, we show here that s-laminin regulates formation of mot or nerve terminals.