Essential roles of the acetylcholine receptor gamma-subunit in neuromuscular synaptic patterning.

Development
Yun LiuWeichun Lin

Abstract

Formation of the vertebrate neuromuscular junction (NMJ) takes place in a stereotypic pattern in which nerves terminate at select sarcolemmal sites often localized to the central region of the muscle fibers. Several lines of evidence indicate that the muscle fibers may initiate postsynaptic differentiation independent of the ingrowing nerves. For example, nascent acetylcholine receptors (AChRs) are pre-patterned at select regions of the muscle during the initial stage of neuromuscular synaptogenesis. It is not clear how these pre-patterned AChR clusters are assembled, and to what extent they contribute to pre- and post-synaptic differentiation during development. Here, we show that genetic deletion of the AChR gamma-subunit gene in mice leads to an absence of pre-patterned AChR clusters during initial stages of neuromuscular synaptogenesis. The absence of pre-patterned AChR clusters was associated with excessive nerve branching, increased motoneuron survival, as well as aberrant distribution of acetylcholinesterase (AChE) and rapsyn. However, clustering of muscle specific kinase (MuSK) proceeded normally in the gamma-null muscles. AChR clusters emerged at later stages owing to the expression of the AChR epsilon-subunit, but the...Continue Reading

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Citations

Jan 19, 2010·Proceedings of the National Academy of Sciences of the United States of America·Fujun ChenWeichun Lin
May 26, 2010·Proceedings of the National Academy of Sciences of the United States of America·Mahru C AnKuo-Fen Lee
Jul 3, 2013·Proceedings of the National Academy of Sciences of the United States of America·Benjamin R NelsonEric N Olson
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Apr 7, 2009·Developmental Biology·Yun LiuWeichun Lin
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