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

Neuregulin-1 (NRG-1) signaling has been implicated in inductive interaction s between pre- and postsynaptic partners during synaptogenesis. We used gen e targeting to selectively disrupt (c) under bar ysteine-(r) under bar ich (d) under bar omain(CRD-) containing NRG-1 isoforms. In CRD-NRG-1(-/-) mice , peripheral projections defasciculated and displayed aberrant branching pa tterns within their targets. Motor nerve terminals were transiently associa ted with broad bands of postsynaptic ACh receptor (AChR) clusters. Initiall y, Schwann cell precursors accompanied peripheral projections, but later, S chwann cells were absent from axons in the periphery. Following initial sta ges of synapse formation, sensory and motor nerves withdrew and degenerated . Our data demonstrate the essential role of CRD-NRG-1-mediated signaling f or coordinating nerve, target, and Schwann cell interactions in the normal maintenance of peripheral synapses, and ultimately in the survival of CRD-N RG-1-expressing neurons.