Cysteine-rich Domain Isoforms of the neuregulin-1 Gene Are Required for Maintenance of Peripheral Synapses

Neuron. 2000 Jan;25(1):79-91. doi: 10.1016/s0896-6273(00)80873-9.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Communication / physiology
  • Cell Survival / physiology
  • Cysteine / chemistry
  • Female
  • Gene Expression Regulation, Developmental
  • Isomerism
  • Lung / innervation
  • Lung / physiology
  • Male
  • Mice
  • Mice, Knockout
  • Motor Neurons / chemistry
  • Motor Neurons / cytology
  • Motor Neurons / physiology*
  • Muscle, Skeletal / innervation
  • Muscle, Skeletal / physiology
  • Mutagenesis / physiology
  • Nerve Degeneration / genetics
  • Nerve Degeneration / physiopathology
  • Neuregulin-1 / chemistry*
  • Neuregulin-1 / genetics
  • Neuregulin-1 / metabolism
  • Neuroglia / cytology
  • Neuroglia / physiology
  • Neurons, Afferent / chemistry
  • Neurons, Afferent / cytology
  • Neurons, Afferent / physiology*
  • Phrenic Nerve / chemistry
  • Phrenic Nerve / cytology
  • Phrenic Nerve / immunology
  • Recombinant Proteins / genetics
  • Respiratory Mechanics
  • Rhombencephalon / embryology
  • Rhombencephalon / pathology
  • Schwann Cells / cytology
  • Schwann Cells / physiology
  • Signal Transduction / physiology*
  • Synapses / chemistry*
  • Synapses / physiology
  • Transcription, Genetic / physiology

Substances

  • Neuregulin-1
  • Recombinant Proteins
  • Cysteine