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* Department of Anatomy and Neurobiology, Laminins, heterotrimers of Department of Internal Medicine, Washington University School of Medicine, St.
Louis, Missouri 63110; and § Division of Neuroscience, Beckman Research Institute of the City of Hope, Duarte, California 91010
, 
, and 
chains, are prominent constituents of basal laminae
(BLs) throughout the body. Previous studies have
shown that laminins affect both myogenesis and synaptogenesis in skeletal muscle. Here we have studied the
distribution of the 10 known laminin chains in muscle
and peripheral nerve, and assayed the ability of several
heterotrimers to affect the outgrowth of motor axons.
We show that cultured muscle cells express four different chains (1, 2, 4, and 5), and that developing
muscles incorporate all four into BLs. The portion of
the muscle's BL that occupies the synaptic cleft contains at least three chains and two chains, but each
is regulated differently. Initially, the 2, 4, 5, and 1
chains are present both extrasynaptically and synaptically, whereas 2 is restricted to synaptic BL from its
first appearance. As development proceeds, 2 remains
broadly distributed, whereas 4 and 5 are lost from
extrasynaptic BL and 1 from synaptic BL. In adults,
4 is restricted to primary synaptic clefts whereas 5 is
present in both primary and secondary clefts. Thus,
adult extrasynaptic BL is rich in laminin 2 (211),
and synaptic BL contains laminins 4 (221), 9 (421), and 11 (521). Likewise, in cultured muscle cells, 2 and 1 are broadly distributed but 5 and
2 are concentrated at acetylcholine receptor-rich "hot spots," even in the absence of nerves. The endoneurial
and perineurial BLs of peripheral nerve also contain
distinct laminin chains: 2, 1, 1, and 4, 5, 2, 1,
respectively. Mutation of the laminin 2 or 2 genes in
mice not only leads to loss of the respective chains in
both nerve and muscle, but also to coordinate loss and compensatory upregulation of other chains. Notably,
loss of 2 from synaptic BL in 2
/ "knockout" mice is
accompanied by loss of 5, and decreased levels of 2
in dystrophic 2dy/dy mice are accompanied by compensatory retention of 4. Finally, we show that motor axons respond in distinct ways to different laminin heterotrimers: they grow freely between laminin 1 (111) and laminin 2, fail to cross from laminin 4 to
laminin 1, and stop upon contacting laminin 11. The
ability of laminin 11 to serve as a stop signal for growing axons explains, in part, axonal behaviors observed
at developing and regenerating synapses in vivo.
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