XSEB4R, a novel RNA-binding protein involved in retinal cell differentiation downstream of bHLH proneural genes
XSEB4R, a novel RNA-binding protein involved in retinal cell differentiation downstream of bHLH proneural genes
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DOI：
10.1242/dev.00983
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发表时间：
2004-02-01
期刊：
影响因子：
4.6
通讯作者：
Perron, M
中科院分区：
文献类型：
--
作者：
Boy, S;Souopgui, J;Perron, M
RNA结合蛋白在基因表达的转录后调控中起着关键作用，但到目前为止，它们在发育过程中还没有得到广泛的研究。我们报告了一种新的RNA结合蛋白XSEB 4 R的分子克隆和时空表达，该蛋白在神经系统中强烈表达。本研究的重点是分析Xseb 4 R在原发性神经发生和视网膜发生的背景下。为了研究Xseb 4 R在眼睛发育过程中的功能，我们建立了一种新的方案，允许在体内脂质转染反义吗啉代寡核苷酸进入视网膜。由此产生的XSEB 4 R敲低导致神经元分化受损，神经胶质细胞数量增加。相比之下，我们的功能获得性分析表明，Xseb 4 R强烈促进神经分化。我们也发现了类似的功能，在初级神经发生。与这种前神经效应一致，我们发现在开放的神经板中，Xseb 4 R的表达被前神经基因XNgnr 1以及分化基因XNeuroD上调，但被Notch/Delta途径抑制。总而言之，我们的研究结果首次表明了参与视网膜发生遗传网络的RNA结合蛋白的前神经效应。
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.