Boy Sébastien, Souopgui Jacob, Amato Marcos A, Wegnez Maurice, Pieler Tomas, Perron Muriel
Laboratoire d'Embryologie Moléculaire et Expérimentale, UMR CNRS 8080, Bâtiment 445, Université Paris XI, 91405 Orsay, France.
Development. 2004 Feb;131(4):851-62. doi: 10.1242/dev.00983. Epub 2004 Jan 21.
RNA-binding proteins play key roles in the post-transcriptional regulation of gene expression but so far they have not been studied extensively in the context of developmental processes. We report on the molecular cloning and spatio-temporal expression of a novel RNA-binding protein, XSEB4R, which is strongly expressed in the nervous system. This study is focused on the analysis of Xseb4R in the context of primary neurogenesis and retinogenesis. To study Xseb4R function during eye development, we set up a new protocol allowing in vivo lipofection of antisense morpholino oligonucleotides into the retina. The resulting XSEB4R knockdown causes an impairment of neuronal differentiation, with an increase in the number of glial cells. By contrast, our gain-of-function analysis demonstrates that Xseb4R strongly promotes neural differentiation. We also showed a similar function during primary neurogenesis. Consistent with this proneural effect, we found that in the open neural plate Xseb4R expression is upregulated by the proneural gene XNgnr1, as well as by the differentiation gene XNeuroD, but is inhibited by the Notch/Delta pathway. Altogether, our results suggest for the first time a proneural effect for a RNA-binding protein involved in the genetic network of retinogenesis.
RNA结合蛋白在基因表达的转录后调控中发挥关键作用，但迄今为止，它们在发育过程中的研究还不够广泛。我们报道了一种新型RNA结合蛋白XSEB4R的分子克隆及时空表达情况，该蛋白在神经系统中强烈表达。本研究聚焦于在初级神经发生和视网膜发生的背景下对Xseb4R进行分析。为了研究Xseb4R在眼睛发育过程中的功能，我们建立了一种新方法，可将反义吗啉代寡核苷酸体内脂质转染到视网膜中。由此导致的XSEB4R敲低会引起神经元分化受损，胶质细胞数量增加。相比之下，我们的功能获得分析表明，Xseb4R强烈促进神经分化。我们还在初级神经发生过程中显示出类似的功能。与这种促神经作用一致，我们发现，在开放神经板中，Xseb4R的表达受促神经基因XNgnr1以及分化基因XNeuroD上调，但受Notch/Delta信号通路抑制。总之，我们的结果首次表明，一种参与视网膜发生基因网络的RNA结合蛋白具有促神经作用。
