Neuromuscular junctions develop through a series of reciprocal interactions between the muscle fiber and the incoming motor neuron. Both agrin and neuregulin have been implicated in neuromuscular junction development. Escher et al. use targeted gene ablations to clarify which molecules act when. It seems that neuregulins are not critical for neuromuscular junction formation but agrin is. The previously observed effects of neuregulin signaling disruptions on neuromuscular junction formation may well have been mediated indirectly through the effects of neuregulins on Schwann cells, which surround the neuromuscular junction.
P. Escher, E. Lacazette, M. Courtet, A. Blindenbacher, L. Landmann, G. Bezakova, K. C. Lloyd, U. Mueller, H. R. Brenner, Synapses form in skeletal muscles lacking neuregulin receptors. Science 308, 1920-1923 (2005). [Abstract] [Full Text]