title: A gene regulation network controlled by Celf1 protein-rbpj mRNA interaction in Xenopus somite segmentation.
abstract: Somite segmentation is impaired in Xenopus celf1 morphant embryos. The Celf1 RNA-binding protein targets bound mRNAs for rapid degradation, and antisense approaches demonstrated that segmentation defects in celf1 morphants were due to a derepression of rbpj mRNA. Rbpj protein is a key player of Notch signalling. Because segmentation involves complex cross-talk between several signalling pathways, we analysed how rbpj derepression impacted these pathways. We found that rbpj derepression stimulated the Notch pathway. Notch positively controlled the expression of cyp26a, which encodes a retinoic acid (RA)-degrading enzyme. Thus, rbpj derepression led to cyp26a overexpression and RA attenuation. It also repressed fgf8, consistent with an inhibition of FGF signalling. Pharmacological inhibition of the FGF pathway repressed cyp26a, but rbpj derepression was sufficient to restore cyp26a expression. Hence, while it was known that the FGF pathway antagonized RA signalling through expression of cyp26a, our results suggest that Rbpj mediates this antagonism. Furthermore, they show that the post-transcriptional repression exerted by Celf1 on rbpj mRNA is required to keep cyp26a expression under the control of FGF signalling. We conclude that rbpj repression by Celf1 is important to couple the FGF and RA pathways in Xenopus segmentation.
authors.affiliation: Université de Rennes 1, Université Européenne de Bretagne , Biosit, CS 34317, 35043 Rennes Cedex , France ; CNRS UMR 6290 Institut de Génétique et Développement de Rennes , CS 34317, 35043 Rennes Cedex , France ; Institut de Biologie du Développement de Marseille, Aix-Marseille Université , CNRS UMR7288, Case 907, 13288 Marseille Cedex 09 , France.
authors.forename: Marie
authors.initials: M
authors.lastname: Cibois
authors.forename: Carole
authors.initials: C
authors.lastname: Gautier-Courteille
authors.forename: Laurent
authors.initials: L
authors.lastname: Kodjabachian
authors.forename: Luc
authors.initials: L
authors.lastname: Paillard
keywords: Cyp26a; FGF; Notch; RNA-binding protein; retinoic acid