Severe neuropathies in mice with targeted mutations in the ErbB3 receptor

  title={Severe neuropathies in mice with targeted mutations in the ErbB3 receptor},
  author={Dieter Riethmacher and Eva Sonnenberg-Riethmacher and Volker Brinkmann and Tomoichiro Yamaai and Gary R. Lewin and Carmen Birchmeier},
Neuregulins and their specific receptors, members of the ErbB family of tyrosine kinases, have been implicated in the control of growth and development of Schwann cells, specialized cells that wrap around nerve axons to provide electrical insulation. Here we use gene targeting to generate mice that lack ErbB3, a high-affinity neuregulin receptor. Homozygous erbB3 mutant embryos lack Schwann-cell precursors and Schwann cells that accompany peripheral axons of sensory and motor neurons. The… 
Aberrant development of motor axons and neuromuscular synapses in erbB2-deficient mice.
It is shown that there are pre- and postsynaptic defects of developing NMJ in erbB2-deficient embryos, and it is demonstrated that erBB2 is essential for in vivo development of the NMJ.
A Dual Role of erbB2 in Myelination and in Expansion of the Schwann Cell Precursor Pool
The thickness of the myelin sheath is determined by the axon diameter, and it is suggested that trophic signals provided by the nerve determine the number of times a Schwann cell wraps an axon.
In vivo knockdown of ErbB3 in mice inhibits Schwann cell precursor migration.
Neuregulin 1–erbB Signaling Is Necessary for Normal Myelination and Sensory Function
Results suggest that disruption of the NRG1–erbB signaling pathway could contribute to the pathogenesis of peripheral neuropathies with hypomyelination and neuropathic pain.
Survival of Adult Spiral Ganglion Neurons Requires erbB Receptor Signaling in the Inner Ear
The data indicate that adult cochlear supporting cells provide critical trophic support to the neurons, that survival of postnatal co chlear sensory neurons depends on reciprocal interactions between neurons and supporting cells, and that these interactions are mediated by NRG and neurotrophins.
Modulation of dorsal root ganglion development by ErbB signaling and the scaffold protein Sorbs3
This work isolated a mutant, ouchless, that specifically fails to develop DRG neurons, although other NC derivatives develop normally, and proposes a model in which Sorbs3 helps to integrate ErbB signals to promote DRG neurogenesis through the activation of MAPK and upregulation of neurogenin1.


Requirement for neuregulin receptor erbB2 in neural and cardiac development
The results demonstrate the importance of erbB2 in neural and cardiac development and find that mutant embryos die before Ell, probably as a result of dysfunctions associated with a lack of cardiac trabeculae.
Multiple essential functions of neuregulin in development
It is shown that neUREgulin -/ - embryos die during embryogenesis and display heart malformations, and the phenotype demonstrates that in vivo neuregulin acts locally and frequently in a paracrine manner.
In vivo effects of neurotrophin-3 during sensory neurogenesis.
It is found that early, but not late, applications of neurotrophin-3 lead to a marked decrease in neuronal numbers in peripheral sensory ganglia, and this decrease is accompanied by, and might result from, a decrease in the number of proliferating neuroblasts in sensoryganglia of treated embryos.
Distinct isoforms of neuregulin are expressed in mesenchymal and neuronal cells during mouse development.
  • D. MeyerC. Birchmeier
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1994
In vivo data indicate in vivo a dual role for neuregulin as mesenchymal and neuronal factor, which has implications on the molecular mechanism by which amplification of c-neu can affect tumor progression of carcinomas.
Isoform-specific expression and function of neuregulin.
It is shown here that targeted mutations that affect different isoforms result in distinct phenotypes, demonstrating that isoforms can take over specific functions in vivo.
Myelin mutants: Model systems for the study of normal and abnormal myelination
  • I. Griffiths
  • Biology
    BioEssays : news and reviews in molecular, cellular and developmental biology
  • 1996
With the major developments in gene mapping and cloning it is now relevant to study mutations in a variety of species with the real prospect of defining their molecular basis.
Neural expression and chromosomal mapping of Neu differentiation factor to 8p12-p21.
In situ hybridization analyses to determine mRNA distribution in the mouse embryo and to map the NDF gene to human karyotypes were performed and it was found that in 14.5-day-postcoitum mouse embryos, NDF expression is confined predominantly to the central and peripheral nervous system.