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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Lin, L.-F. H., Doherty, D. H., Lile, J. D., Bektesh, S. & Collins, F. Science 260, 1130–1132 (1993).
Tomac, A. et al. Nature 373, 335–339 (1995).
Beck, K. D. et al. Nature 373, 339–341 (1995).
Henderson, C. E. et al. Science 266, 1062–1064 (1994).
Yan, Q., Matheson, C. & Lopez, O. T. Nature 373, 341–344 (1995).
Oppenheim, R. W. et al. Nature 373, 344–346 (1995).
Trupp, M. et al. J. Cell Biol. 130, 137–148 (1995).
Buj-Bello, A., Buchman, V. L., Horton, A., Rosenthal, A. & Davies, A. M. Neuron 15, 821–828 (1995).
Arenas, E., Trupp, M., Åkerud, P. & Ibáñez, C. Neuron 15, 1465–1473 (1995).
Mount, H. T. J., Dean, D. O., Alberch, J., Dreyfus, C. F. & Black, I. B. Proc. natn. Acad. Sci. U.S.A. 92, 9092–9096 (1995).
Poulsen, K. T. et al. Neuron 13, 1245–1252 (1994).
Gash, D. M. et al. Nature 380, 252–255 (1996).
Hellmich, H. L., Kos, L., Cho, E. S., Mahon, K. A. & Zimmer, A. Mech. Dev. 54, 95–105 (1996).
Suvanto, P. et al. Eur. J. Neurosci. 8, 816–822 (1996).
Saxén, L. Organogenesis of the Kidney (Cambridge Univ. Press, 1987).
Ekblom, P. FASEB J. 3, 2141–2150 (1989).
Yntenna, C. L. & Hammond, W. S. J. comp. Neurol. 101, 515–542 (1954).
Le Douarin, N. M. & Teillet, M.-A. J. Embryol. exp. Morphol. 30, 31–48 (1973).
Pachnis, V., Mankoo, B. & Costantini, F. Development 119, 1005–1017 (1993).
Schuchardt, A., D'Agati, V., Larsson-Blomberg, L., Costantini, F. & Pachnis, V. Nature 367, 380–383 (1994).
Durbec, P. L., Larsson-Blomberg, L. B., Schuchardt, A., Costantini, F. & Pachnis, V. Development 122, 349–358 (1996).
Pasini, B., Cecchenni, I. & Romeo, G. Trends Genet. 12, 138–144 (1996).
Osathanondh, V. & Potter, E. L. Archs Path. 82, 391–402 (1966).
Tybulewicz, V. L. J., Crawford, C. E., Jackson, P. K., Bronson, R. T. & Mulligan, R. C. Cell 65, 1153–1163 (1991).
Li, E., Bestor, T. H. & Jaenisch, R. Cell 69, 915–926 (1992).
Nagy, A., Rossant, J., Nagy, R., Abramow-Newerly, W. & Roder, J. C. Proc. natn. Acad. Sci. U.S.A. 90, 8424–8428 (1993).
Love, P. E., Tremblay, M. & Westphal, H. Proc. natn. Acad. Sci. U.S.A. 89, 9929–9933 (1992).
Sariola, H., Holm, K. & Henke-Fahle, S. Development 104, 589–599 (1988).
Vainio, S., Karavanova, I., Jowett, A. & Thesleff, I. Cell 75, 45–58 (1993).
Harlow, E. & Lane, D. Antibodies. A Laboratory Manual (Cold Spring Harbour Laboratory Press, NY, 1988).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/382073a0
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.