Abstract
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 cells1,2,3, 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 receptor4,5,6. Homozygous erbB3 mutant embryos lack Schwann-cell precursors and Schwann cells that accompany peripheral axons of sensory and motor neurons. The initial development of motor neurons and sensory neurons of dorsal root ganglia occurs as it should, but at later stages most motor neurons (79%) and sensory neurons in dorsal root ganglia (82%) undergo cell death in erbB3 mutant embryos. Degeneration of the peripheral nervous system in erbB3 mutant pups is thus much more severe than the cell death in mice that lack neurotrophins or neurotrophin receptors7,8. We also show that ErbB3 functions in a cell-autonomous way during the development of Schwann cells, but not in the survival of sensory or motor neurons. Our results indicate that sensory and motor neurons require factors for their survival that are provided by developing Schwann cells.
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Acknowledgements
We thank A. Rehaus for technical assistance; W. Birchmeier and A. Garratt for critical reading of the manuscript; Y. Yarden for human ErbB3 cDNA; M.-M. Portier for the gift of polyclonal anti-peripherin antibodies; R. Mirsky for P0 cDNA; and H. Geldeblom for use of the electron microscope facility. This work was upported by grants from the German Israeli Foundation, the Deutsche Forschungsgemeinschaft, and the BMBF to C.B., and by a grant from the Deutsche Forschungsgemeinschaft to G.R.L.
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Riethmacher, D., Sonnenberg-Riethmacher, E., Brinkmann, V. et al. Severe neuropathies in mice with targeted mutations in the ErbB3 receptor. Nature 389, 725–730 (1997). https://doi.org/10.1038/39593
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DOI: https://doi.org/10.1038/39593
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