Neuregulin1 displayed on motor axons regulates terminal Schwann cell-mediated synapse elimination at developing neuromuscular junctions

Young Il Lee, Yue Li, Michelle Mikesh, Ian Smith, Klaus Armin Nave, Markus H. Schwab, Wesley J. Thompson

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

Synaptic connections in the nervous system are rearranged during development and in adulthood as a feature of growth, plasticity, aging, and disease. Glia are implicated as active participants in these changes. Here we investigated a signal that controls the participation of peripheral glia, the terminal Schwann cells (SCs), at the neuromuscular junction (NMJ) in mice. Transgenic manipulation of the levels of membrane-tethered neuregulin1 (NRG1-III), a potent activator of SCs normally presented on motor axons, alters the rate of loss of motor inputs at NMJs during developmental synapse elimination. In addition, NMJs of adult transgenic mice that expressed excess axonal NRG1-III exhibited continued remodeling, in contrast to the more stable morphologies of controls. In fact, synaptic SCs of these adult mice with NRG1-III overexpression exhibited behaviors evident in wild type neonates during synapse elimination, including an affinity for the postsynaptic myofiber surface and phagocytosis of nerve terminals. Given that levels of NRG1-III expression normally peak during the period of synapse elimination, our findings identify axon-tethered NRG1 as a molecular determinant for SC-driven neuromuscular synaptic plasticity.

Original languageEnglish (US)
Pages (from-to)E479-E487
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number4
DOIs
StatePublished - Jan 26 2016
Externally publishedYes

Keywords

  • Neuregulin1
  • Neuromuscular junction
  • Schwann cell
  • Synapse elimination
  • Synaptic competition

ASJC Scopus subject areas

  • General

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