MuSK controls where motor axons grow and form synapses.
Motor axons approach muscles that are regionally prespecialized, as acetylcholine receptors are clustered in the central region of muscle before and independently of innervation. This muscle prepattern requires MuSK, a receptor tyrosine kinase that is essential for synapse formation. It is not known how muscle prepatterning is established, and whether motor axons recognize this prepattern. Here we show that expression of Musk is prepatterned in muscle and that early Musk expression in developing myotubes is sufficient to establish muscle prepatterning. We further show that ectopic Musk expression promotes ectopic synapse formation, indicating that muscle prepatterning normally has an instructive role in directing where synapses will form. In addition, ectopic Musk expression stimulates synapse formation in the absence of Agrin and rescues the lethality of Agrn mutant mice, demonstrating that the postsynaptic cell, and MuSK in particular, has a potent role in regulating the formation of synapses.
Kim
Natalie
N
Molecular Neurobiology Program, The Helen L and Martin S Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, New York University Medical School, New York, NY 10016, USA.
Burden
Steven J
SJ
D018171:Agrin / Q000172:deficiency; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000502:physiology*; D019521:Body Patterning / Q000235:genetics; D051927:CD24 Antigen / Q000235:genetics; D002478:Cells, Cultured; D003964:Diaphragm / Q000166:cytology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000166:cytology*; D018482:Muscle, Skeletal / Q000166:cytology; D009154:Mutation; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011950:Receptors, Cholinergic / Q000378:metabolism; D013569:Synapses / Q000502:physiology*
D018171:Agrin; D051927:CD24 Antigen; C497890:Cd24a protein, mouse; D011950:Receptors, Cholinergic; D049452:Green Fluorescent Proteins; C511695:MuSK protein, mouse; D020794:Receptor Protein-Tyrosine Kinases