视黄酸信号转导的机制及其在器官和肢体发育中的作用。
Mechanisms of retinoic acid signalling and its roles in organ and limb development.
机构信息
Development, Aging, and Regeneration Program, Sanford-Burnham Medical Research Institute, 10901 N. Torrey Pines Road, La Jolla, California 92037, USA.
出版信息
Nat Rev Mol Cell Biol. 2015 Feb;16(2):110-23. doi: 10.1038/nrm3932. Epub 2015 Jan 5.
Abstract
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.
摘要
视黄酸（RA）信号在脊椎动物发育过程中起着核心作用。在特定位置合成的 RA 通过与核 RA 受体（RAR）相互作用来调节转录，这些受体与靶基因附近的 RA 反应元件（RARE）结合。RA 最初是基于其对肢体发育的致畸作用而被认为具有信号转导作用的。后来的遗传研究表明，内源性 RA 通过抑制成纤维细胞生长因子 8（Fgf8）来促进前肢起始。对 RA 在肢体中的功能的深入了解为理解 RA 如何调节其他发育过程提供了范例。体内研究已经确定了 RARE，它们在身体轴延伸过程中控制 Fgf8 的抑制，或在神经元分化和器官发生过程中激活同源盒（Hox）基因和其他关键调节剂。
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本文引用的文献
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Development. 2014 Aug;141(15):2972-7. doi: 10.1242/dev.112367.
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Active repression by RARγ signaling is required for vertebrate axial elongation.RARγ 信号的主动抑制对于脊椎动物的轴向伸长是必需的。
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