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Aberrant neural and cardiac development in mice lacking the ErbB4 neuregulin receptor

Nature volume 378, pages 390394 (23 November 1995) | Download Citation

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Abstract

VARIOUS in vitro studies have suggested that ErbB4 (HER4) is a receptor for the neuregulins, a family of closely related proteins implicated as regulators of neural and muscle development, and of the differentiation and oncogenic transformation of mammary epithelia1–3. Here we demonstrate that ErbB4 is an essential in vivo regulator of both cardiac muscle differentiation and axon guidance in the central nervous system (CNS). Mice lacking ErbB4 die during mid-embryogenesis from the aborted development of myocardial trabeculae in the heart ventricle. They also display striking alterations in innervation of the hindbrain in the CNS that are consistent with the restricted expression of the ErbB4 gene in rhombomeres 3 and 5. Similarities in the cardiac phenotype of ErbB4 and neuregulin gene mutants suggest that ErbB4 functions as a neuregulin receptor in the heart; however, differences in the hindbrain phenotypes of these mutants are consistent with the action of a new ErbB4 ligand in the CNS.

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Author information

Affiliations

  1. Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA

    • Martin Gassmann
    • , Horst Simon
    •  & Greg Lemke
  2. Differentiation Program, European Molecular Biology Laboratory,69012 Heidelberg, Germany

    • Franca Casagranda
    • , Donata Orioli
    •  & Rüdiger Klein
  3. Department of Neuropharmacology, Scripps Research Institute,La Jolla, California 92037, USA

    • Cary Lai

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https://doi.org/10.1038/378390a0

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