Mechanisms of retinoic acid signalling and its roles in organ and limb development.
Mechanisms of retinoic acid signalling and its roles in organ and limb development.
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DOI：
10.1038/nrm3932
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发表时间：
2015-02
期刊：
影响因子：
--
通讯作者：
Duester G
中科院分区：
文献类型：
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作者：
Cunningham TJ;Duester G
视黄酸（RA）信号传导在脊椎动物发育过程中具有核心作用。在特定位置合成的RA通过与靶基因附近的RA反应元件（RARE）结合的核RA受体（RAR）相互作用来调节转录。RA首先涉及信号的基础上，其致畸作用对肢体发育。后来的遗传学研究表明，内源性RA通过抑制成纤维细胞生长因子8（Fgf8）促进前肢起始。对RA肢体功能的深入了解可以作为理解RA如何调节其他发育过程的范例。体内研究已经鉴定了在体轴延伸期间控制Fgf8的抑制或在神经元分化和器官发生期间控制同源异型盒（Hox）基因和其他关键调节因子的激活的RARE。
Retinoic acid (RA) signalling has a central role during vertebrate development. RA synthesized in specific locations regulates transcription by interacting with nuclear RA receptors (RARs) bound to RA response elements (RAREs) near target genes. RA was first implicated in signalling on the basis of its teratogenic effects on limb development. Genetic studies later revealed that endogenous RA promotes forelimb initiation by repressing fibroblast growth factor 8 (Fgf8). Insights into RA function in the limb serve as a paradigm for understanding how RA regulates other developmental processes. In vivo studies have identified RAREs that control repression of Fgf8 during body axis extension or activation of homeobox (Hox) genes and other key regulators during neuronal differentiation and organogenesis.