Cysteine-rich domain isoforms of the Neuregulin-1 gene are required for maintenance of peripheral synapses

Deon Wolpowitz, Thornton B.A. Mason, Paula Dietrich, Monica Mendelsohn, David A. Talmage, Lorna W. Role

Research output: Contribution to journalArticle

219 Citations (Scopus)

Abstract

Neuregulin-1 (NRG-1) signaling has been implicated in inductive interactions between pre- and postsynaptic partners during synaptogenesis. We used gene targeting to selectively disrupt cysteine-rich domain-(CRD-) containing NRG-1 isoforms. In CRD-NRG-1(-/-) mice, peripheral projections defasciculated and displayed aberrant branching patterns within their targets. Motor nerve terminals were transiently associated with broad bands of postsynaptic ACh receptor (AChR) clusters. Initially, Schwann cell precursors accompanied peripheral projections, but later, Schwann cells were absent from axons in the periphery. Following initial stages of synapse formation, sensory and motor nerves withdrew and degenerated. Our data demonstrate the essential role of CRD-NRG-1-mediated signaling for coordinating nerve, target, and Schwann cell interactions in the normal maintenance of peripheral synapses, and ultimately in the survival of CRD- NRG-1-expressing neurons.

Original languageEnglish (US)
Pages (from-to)79-91
Number of pages13
JournalNeuron
Volume25
Issue number1
DOIs
StatePublished - Jan 1 2000

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Neuregulin-1
Synapses
Cysteine
Protein Isoforms
Maintenance
Schwann Cells
Genes
Neurons
Gene Targeting
Cholinergic Receptors
Cell Communication
Axons

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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Cysteine-rich domain isoforms of the Neuregulin-1 gene are required for maintenance of peripheral synapses. / Wolpowitz, Deon; Mason, Thornton B.A.; Dietrich, Paula; Mendelsohn, Monica; Talmage, David A.; Role, Lorna W.

In: Neuron, Vol. 25, No. 1, 01.01.2000, p. 79-91.

Research output: Contribution to journalArticle

Wolpowitz, Deon ; Mason, Thornton B.A. ; Dietrich, Paula ; Mendelsohn, Monica ; Talmage, David A. ; Role, Lorna W. / Cysteine-rich domain isoforms of the Neuregulin-1 gene are required for maintenance of peripheral synapses. In: Neuron. 2000 ; Vol. 25, No. 1. pp. 79-91.
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