Fig. 1.

Critical periods of NMJ development with a focus on the elimination of multi-innervation. Motoneurons emit axons toward myotubes from E10 to E15 in mice. In parallel, Schwann cells migrate to reach the NMJ from E16 and cap the terminal. The differentiation of myoblasts into myotubes and muscle fibers is also schematized altogether with the time course. Dispersed acetylcholine receptors (AChRs) are expressed at moderate levels throughout myotubes surface prior to synapse formation, from E15 at the period of polyneuronal innervation, i.e. when each muscle fiber is still innervated by one or several axons of motor neurons (MNs). Postnatally, a critical step with the redrawal of about half multi-innervation occurs between P0 to P7, and the process of synapse elimination is achieved 2 weeks postnatally. AChR clustering occurs in the post-synaptic membrane, altogether with a progressive transition from multiple to single innervation of the NMJ