GDNF signalling through the Ret receptor tyrosine kinase
- 1 June 1996
- journal article
- Published by Springer Nature in Nature
- Vol. 381 (6585) , 789-793
- https://doi.org/10.1038/381789a0
Abstract
Mutational analysis in humans and mice has demonstrated that the Ret, the product of the c-ret proto-oncogene, a member of the receptor tyrosine kinase (RTK) superfamily, is essential for development of the enteric nervous system and kidney. 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), a distant member of the transforming growth factor (TGF)-beta superfamily, signals through the Ret RTK. Furthermore, using explant cultures from wild-type and Ret-deficient mouse embryos, 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 neurons, has profound effects on kidney organogenesis and the development of the peripheral nervous system.Keywords
This publication has 26 references indexed in Scilit:
- Mesoderm induction in Xenopus caused by activation of MAP kinaseNature, 1995
- In vivo neurotrophic effects of GDNF on neonatal and adult facial motor neuronsNature, 1995
- Mesencephalic dopaminergic neurons protected by GDNF from axotomy-induced degeneration in the adult brainNature, 1995
- Protection and repair of the nigrostriatal dopaminergic system by GDNF in vivoNature, 1995
- Developing motor neurons rescued from programmed and axotomy-induced cell death by GDNFNature, 1995
- GDNF: a Potent Survival Factor for Motoneurons Present in Peripheral Nerve and MuscleScience, 1994
- Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor RetNature, 1994
- Mutations of the RET proto-oncogene in Hirschsprung's diseaseNature, 1994
- Point mutations affecting the tyrosine kinase domain of the RET proto-oncogene in Hirschsprung's diseaseNature, 1994
- GDNF: a Glial Cell Line-Derived Neurotrophic Factor for Midbrain Dopaminergic NeuronsScience, 1993