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

Neuron | 2000

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.

Pubmed ID: 10707974 RIS Download

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Associated grants

  • Agency: NINDS NIH HHS, United States
    Id: R01 NS029071-12
  • Agency: NINDS NIH HHS, United States
    Id: NS29071
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS029071-15
  • Agency: NIDA NIH HHS, United States
    Id: DA09366
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS029071
  • Agency: NCRR NIH HHS, United States
    Id: 1S10RR10506
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS029071-16
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS029071-14
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS029071-11
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS029071-13
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS029071-17
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS029071-13S1

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