Induction of neuregulin signaling in mouse Schwann cells in vivo mimics responses to denervation

Christopher R. Hayworth, Susan E. Moody, Lewis A. Chodosh, Paul Krieg, Mendell Rimer, Wesley J. Thompson

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

Neuregulins play crucial roles in early development of Schwann cells (SCs), but their roles in the activities of SCs during denervation and reinnervation of muscle are less clear. In the present study, the Tet-On system has been used in transgenic mice to enable inducible expression of a mutant, constitutively active neuregulin receptor (ErbB2) in SCs. This induction simulates neuregulin signaling to these cells. Reporter transgenes were used to show a tightly regulated, SC-selective expression in muscle. Induction leads to a number of changes in SCs at neuromuscular junctions that mimic the response to muscle denervation/reinnervation. These include process extension, soma migration, and proliferation. SCs also come to express nestin, a protein characteristic of their reaction to muscle denervation. This activation of SCs results in the sprouting of nerve terminals, and these sprouts follow the extensions of the SCs. However, these sprouts and their associated SCs disappear after the removal of the inducer. Last, induction of the active receptor is sufficient to rescue SCs in neonatal muscle from denervation-induced apoptosis. These findings show that the responses of SCs in muscle to denervation can be explained by induction of an autocrine/paracrine neuregulin signaling cascade suggested by previous molecular studies.

Original languageEnglish (US)
Pages (from-to)6873-6884
Number of pages12
JournalJournal of Neuroscience
Volume26
Issue number25
DOIs
StatePublished - 2006

Keywords

  • Cell migration
  • Cell proliferation
  • ErbB receptor
  • GGF
  • Nestin
  • Neu
  • Neuromuscular junction
  • S100B
  • Sprouting
  • Terminal Schwann cell
  • Tet-On
  • rtTA

ASJC Scopus subject areas

  • Neuroscience(all)

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