Regulation of c-ret expression by retinoic acid in rat metanephros
: implication in nephron mass control.
Moreau, Evelyne, Jos[acute]e Vilar, Martine Lelievre-Pegorier, Claudie
Merlet-Benichou, and Thierry Gilbert.
INSERM U319 "D[acute]eveloppement normal et pathologique des
fonctions [acute]epith[acute]eliales", Universit[acute]e Paris 7
-Denis Diderot, 2 Place Jussieu, 75005 Paris, France
APStracts 5:0158F, 1998.
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.
Received 5 May 1998; accepted in final form 3 September 1998.
APS Manuscript Number F106-8.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 21 September 1998