Abstract
The patterning of skeletal muscle is thought to depend upon signals provided by motor neurons. We show that AChR gene expression and AChR clusters are concentrated in the central region of embryonic skeletal muscle in the absence of innervation. Neurally derived Agrin is dispensable for this early phase of AChR expression, but MuSK, a receptor tyrosine kinase activated by Agrin, is required to establish this AChR prepattern. The zone of AChR expression in muscle lacking motor axons is wider than normal, indicating that neural signals refine this muscle-autonomous prepattern. Neuronal Neuregulin-1, however, is not involved in this refinement process, nor indeed in synapse-specific AChR gene expression. Our results demonstrate that AChR expression is patterned in the absence of innervation, raising the possibility that similarly prepatterned muscle-derived cues restrict axon growth and initiate synapse formation.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Agrin / deficiency
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Agrin / genetics
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Agrin / metabolism
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Animals
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Axons / physiology
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Body Patterning / physiology
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Embryonic and Fetal Development
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Gene Expression Regulation, Developmental*
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Mice
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Mice, Knockout
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Motor Neurons / physiology*
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Muscle Denervation
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Muscle, Skeletal / embryology*
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Muscle, Skeletal / innervation*
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Neuregulins / genetics
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Neuregulins / physiology
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Neurons, Afferent / physiology
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Receptor Protein-Tyrosine Kinases / deficiency
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Receptor Protein-Tyrosine Kinases / genetics
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Receptor Protein-Tyrosine Kinases / metabolism
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / physiology
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Receptors, Cholinergic / genetics*
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Receptors, G-Protein-Coupled*
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Receptors, Lysophospholipid
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Recombination, Genetic
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Synapses / physiology
Substances
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Agrin
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Neuregulins
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Receptors, Cell Surface
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Receptors, Cholinergic
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Receptors, G-Protein-Coupled
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Receptors, Lysophospholipid
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MUSK protein, human
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Receptor Protein-Tyrosine Kinases