Patterning of muscle acetylcholine receptor gene expression in the absenceof motor innervation

The patterning of skeletal muscle is thought to depend upon signals provide d by motor neurons. We show that AChR gene expression and AChR clusters are concentrated in the central region of embryonic skeletal muscle in the abs ence of innervation. Neurally derived Ag rin 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 exp ression in muscle lacking motor axons is wider than normal, indicating that neural signals refine this muscle-autonomous prepattern. Neuronal Neuregul in-1, however, is not involved in this refinement process, nor indeed in sy napse-specific AChR gene expression. Our results demonstrate that AChR expr ession is patterned in the absence of innervation, raising the possibility that similarly prepatterned muscle-derived cues restrict axon growth and in itiate synapse formation.