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GDNF signalling through the Ret receptor tyrosine kinase

Nature volume 381, pages 789–793 (1996)Cite this article

Abstract

MUTATIONAL analysis in humans and mice has demonstrated that Ret, the product of the c-ret proto-oncogene, a member of the receptor tyrosine kinase (RTK) superfamily1, is essential for development of the enteric nervous system and kidney2–6. Despite the established role of Ret in mammalian embryogenesis, its cognate ligand(s) is currently unknown. Here we demonstrate, by using a Xenopus embryo bioassay, that glial-cell-line-derived neurotrophic factor (GDNF)7, a distant member of the transforming growth factor(TGF)-β superfamily, signals through the Ret RTK. Furthermore, using explant cultures from wild-type and Ret-deficient mouse embryos4, we show that normal c-ret function is necessary for GDNF signalling in the peripheral nervous system. Our data strongly suggest that Ret is a functional receptor for GDNF, and that GDNF, in addition to its potential role in the differentiation and survival of central nervous system neurons8–12, has profound effects on kidney organogenesis and the development of the peripheral nervous system.

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Authors and Affiliations

  1. Division of Developmental Neurobiology, National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK

    Pascale Durbec, Camelia V. Marcos-Gutierrez, Carol Kilkenny, Maria Grigoriou & Vassilis Pachnis

  2. Institute of Biotechnology, Biocentre 1, Univesity of Helsinki, Viikinkaari 9, PO Box 56, FIN-00014, Helsinki, Finland

    Kirmo Wartiowaara, Petro Suvanto, Mart Saarma & Hannu Sariola

  3. CRC Human Cancer Genetics Research Group, Addenbrook's Hospital, University of Cambridge, Box 238, Level 3 Lab Block, Hills Road, Cambridge, CB2 2QQ, UK

    Darrin Smith & Bruce Ponder

  4. Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, New York, 10032, USA

    Frank Costantini

  5. Childrens Hospital, University of Helsinki, Stenbackinkatu 11, FIN-000290, Helsinki, Finland

    Hannu Sariola

Authors
  1. Pascale Durbec
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  2. Camelia V. Marcos-Gutierrez
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  3. Carol Kilkenny
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  6. Petro Suvanto
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  7. Darrin Smith
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  9. Frank Costantini
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  12. Vassilis Pachnis
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Durbec, P., Marcos-Gutierrez, C., Kilkenny, C. et al. GDNF signalling through the Ret receptor tyrosine kinase. Nature 381, 789–793 (1996). https://doi.org/10.1038/381789a0

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