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Defects in enteric innervation and kidney development in mice lacking GDNF

Nature volume 382, pages 73–76 (1996)Cite this article

Abstract

GLIAL-CELL-LINE-DERIVED neurotrophic factor (GDNF) has been isolated as a neurotrophic factor for midbrain dopaminergic neurons1. Because of its neurotrophic activity on a wide range of neuronal populations in vitro and in vivo2–11, GDNF is being considered as a potential therapeutic agent for neuronal disorders2,3,12. During mammalian development, it is expressed not only in the nervous system, but also very prominently in the metanephric kidney and the gastrointestinal tract, suggesting possible functions during organogenesis7,11,13,14. We have investigated the role of GDNF during development by generating a null mutation in the murine GDNF locus, and found that mutant mice show kidney agenesis or dysgenesis and defective enteric innervation. We demonstrate that GDNF induces ureter bud formation and branching during metanephros development, and is essential for proper innervation of the gastrointestinal tract.

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Authors and Affiliations

  1. Laboratory of Mammalian Genes and Development, National Institutes of Health, Bethesda, 20892, USA

    José G. Pichel, Liya Shen, Hui Z. Sheng, Alexander Grinberg, Eric J. Lee, Sing Ping Huang & Heiner Westphal

  2. Departments of Pharmacology and Basic Dental Science, University of Colorado Health Sciences Center, Denver, Colorado, 80262, USA

    Ann-Charlotte Granholm & Barry J. Hoffer

  3. Department of Anatomy, Monash University, Clayton, 3168, Victoria, Australia

    John Drago

  4. Programs of Molecular Neurobiology and Developmental Biology, Institute of Biotechnology, Biocentrel, University of Helsinki, Viikinkaari 9, P.O. Box 56, FIN-00014, Helsinki, Finland

    Mart Saarma & Hannu Sariola

  5. Laboratory of Pediatric Pathology, Childrens Hospital, University of Helsinki, Stenbackinkatu 11, FIN-00380, Helsinki, Finland

    Hannu Sariola

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  1. José G. Pichel
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Pichel, J., Shen, L., Sheng, H. et al. Defects in enteric innervation and kidney development in mice lacking GDNF. Nature 382, 73–76 (1996). https://doi.org/10.1038/382073a0

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