title: Aberrant differentiation of neuromuscular junctions in mice lacking s-laminin/laminin beta 2.
abstract: Synapse formation requires a complex interchange of information between the pre- and postsynaptic partners. At the skeletal neuromuscular junction, some of this information is contained in the basal lamina (BL), which runs through the synaptic cleft between the motor nerve terminal and the muscle fibre. During regeneration following injury, components of synaptic BL can trigger several features of postsynaptic differentiation in the absence of the nerve terminal, and of presynaptic differentiation in the absence of the muscle fibre. One nerve-derived component of synaptic BL, agrin, is known to affect postsynaptic differentiation, but no muscle-derived components have yet been shown to influence motor nerve terminals. A candidate for such a role is s-laminin (also called laminin beta 2), a homologue of the B1 (beta 1) chain of the widely distributed BL glycoprotein, laminin. s-Laminin is synthesized by muscle cells and concentrated in synaptic BL. In vitro, recombinant s-laminin fragments are selectively adhesive for motor neuron-like cells, inhibit neurite outgrowth promoted by other matrix molecules, and act as a 'stop signal' for growing neurites. By generating and characterizing mice with a targeted mutation of the s-laminin gene, we show here that s-laminin regulates formation of motor nerve terminals.
authors.affiliation: Department of Anatomy, Washington University Medical School, St Louis, Missouri 63110.
authors.forename: P G
authors.initials: PG
authors.lastname: Noakes
authors.forename: M
authors.initials: M
authors.lastname: Gautam
authors.forename: J
authors.initials: J
authors.lastname: Mudd
authors.forename: J R
authors.initials: JR
authors.lastname: Sanes
authors.forename: J P
authors.initials: JP
authors.lastname: Merlie
mesh_terms: D000200:Action Potentials; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D007797:Laminin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D009046:Motor Neurons / Q000502:physiology / Q000648:ultrastructure; D009154:Mutation; D009469:Neuromuscular Junction / Q000196:embryology* / Q000648:ultrastructure
chemical_list: D007797:Laminin; C058783:laminin beta2