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Am J Physiol Renal Physiol 275: F938-F945, 1998;
0363-6127/98 $5.00
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Vol. 275, Issue 6, F938-F945, December 1998

Regulation of c-ret expression by retinoic acid in rat metanephros: implication in nephron mass control

Evelyne Moreau, José Vilar, Martine Lelièvre-Pégorier, Claudie Merlet-Bénichou, and Thierry Gilbert

Institut National de la Santé et de la Recherche Médicale Unité 319, Développement Normal et Pathologique des Fonctions Epithéliales, Université Paris 7-Denis Diderot, 75251 Paris Cedex 05, France

Vitamin A and its derivatives have been shown to promote kidney development in vitro in a dose-dependent fashion. To address the molecular mechanisms by which all-trans-retinoic acid (RA) may regulate the nephron mass, rat kidneys were removed on embryonic day 14 (E14) and grown in organ culture under standard or RA-stimulated conditions. By using RT-PCR, we studied the expression of the glial cell line-derived neurotrophic factor (GDNF), its cell surface receptor-alpha (GDNFR-alpha ), and the receptor tyrosine kinase c-ret, known to play a major role in renal organogenesis. Expression of GDNF and GDNFR-alpha transcripts was high at the time of explantation and remained unaffected in culture with or without RA. In contrast, c-ret mRNA level, which was low in E14 metanephros and dropped rapidly in vitro, was increased by RA in a dose-dependent manner. The same is true at the protein level. Exogenous GDNF barely promotes additional nephron formation in vitro. Thus the present data establish c-ret as a key target of retinoids during kidney organogenesis.

renal differentiation; all-trans-retinoic acid; c-ret; glial cell line-derived neurotrophic factor; glial cell line-derived neurotrophic factor receptor-alpha


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