Retinoic acid-dependent control of MAP kinase phosphatase-3 is necessary for early kidney development in Xenopus
Article first published online: 21 JUN 2012
Copyright © 2012 Soçiété Francaise des Microscopies and Société de Biologie Cellulaire de France
Biology of the Cell
Volume 104, Issue 9, pages 516–532, September 2012
How to Cite
Le Bouffant, R., Wang, J.-H., Futel, M., Buisson, I., Umbhauer, M. and Riou, J.-F. (2012), Retinoic acid-dependent control of MAP kinase phosphatase-3 is necessary for early kidney development in Xenopus. Biology of the Cell, 104: 516–532. doi: 10.1111/boc.201200005
- Issue published online: 4 SEP 2012
- Article first published online: 21 JUN 2012
- Accepted manuscript online: 2 MAY 2012 03:50AM EST
- Manuscript Accepted: 20 APR 2012
- Manuscript Received: 25 FEB 2012
- Retinoic acid;
In Xenopus, the functional kidney of the tadpole, the pronephros, forms from the kidney field, which is specified at completion of gastrulation. Specification of the kidney field requires retinoic acid (RA) signalling during gastrulation, while fibroblast growth factor (FGF) signals inhibit should be inhibit this process.
We have analysed the functional interactions taking place during gastrulation between RA and FGF signals in the lateral marginal zone (LMZ), that is in the environment of unspecified pronephric mesoderm precursors. Inhibition of FGF receptor (FGFR) signalling with SU5402 does not significantly affect expression of genes encoding RA metabolism enzymes and RA receptor-α in LMZ explants. Furthermore, SU5402 has no effect on the expression of hoxa1, a major RA target in the LMZ, showing that FGF is not antagonising RA in the LMZ. Disruption of RA signalling affects FGF ligand production to some extent, especially FGF8b, but the strongest effect is the down-regulation of the mitogen-activated protein kinase phosphatase-3 (MKP3)-encoding gene, mkp3. A strong up-regulation of mkp3 occurs in response to exogenous RA. This effect is reduced in a context of FGFR inhibition, suggesting that RA and FGF signals are co-operating upstream of mkp3. Mkp3 knockdown results in an inhibition of the kidney field markers pax8 and lhx1 and in a defective development of the pronephros.
FGF is not negatively influencing pronephric specification by antagonising RA signalling. Functional interactions between RA and FGF rather take place at the level of the transcriptional regulation of mkp3, indicating that RA may antagonise FGF signalling at the level of the extracellular signal-regulated kinase (Erk) pathway. A fine tuning of Erk signalling by MKP3 is important for the proper establishment of the kidney field.