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Publication : Cysteine-rich domain isoforms of the neuregulin-1 gene are required for maintenance of peripheral synapses.

First Author  Wolpowitz D Year  2000
Journal  Neuron Volume  25
Issue  1 Pages  79-91
PubMed ID  10707974 Mgi Jnum  J:60159
Mgi Id  MGI:1352924 Doi  10.1016/s0896-6273(00)80873-9
Citation  Wolpowitz D, et al. (2000) Cysteine-rich domain isoforms of the neuregulin-1 gene are required for maintenance of peripheral synapses. Neuron 25(1):79-91
abstractText  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.
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