Retinoic acid signaling in mammalian eye development.

Retinoic acid signaling in mammalian eye development.
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DOI:
10.1016/j.exer.2009.04.012
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发表时间:
2009-09
影响因子:
3.4
通讯作者:
Wang, Wei-Lin
Wang, Wei-Lin
中科院分区:
医学3区
文献类型:
--
作者:
Cvekl, Ales;Wang, Wei-Lin

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视黄酸 (RA) 是维生素 A(视黄醇)的生物活性代谢物,在许多发育和生理过程中充当信号分子。 RA 信号在胚胎眼睛发育过程中发挥多种作用。 RA 信号传导最初是视泡和内陷晶状体基板之间相互作用所必需的。 RA 信号传导通过其在神经嵴细胞衍生的眼周间质中的活动促进腹侧视网膜和视神经的正常发育。 RA 通过调节非类固醇激素受体 RARα/β/γ 和 RXRα/β/γ 家族的生物活性来协调这些过程。这些 DNA 结合转录因子将 DNA 识别为 RAR/RXR 异二聚体,并招募多蛋白转录共阻遏物复合物。 RA 与 RAR 受体的结合诱导受体的构象变化,然后用共激活剂复合物取代共阻遏物。眼周间充质中 RARα/β/γ 受体失活会消除眼前节的形成。这篇综述总结了最近对 RA 信号传导的遗传学研究以及了解与 RAR/RXR 一起发挥作用的转录共激活因子分子机制的进展。
Retinoic acid (RA) is a biologically active metabolite of vitamin A (retinol) that serves as a signaling molecule during a number of developmental and physiological processes. RA signaling plays multiple roles during embryonic eye development. RA signaling is initially required for reciprocal interactions between the optic vesicle and invaginating lens placode. RA signaling promotes normal development of the ventral retina and optic nerve through its activities in the neural crest cell-derived periocular mesenchyme. RA coordinates these processes by regulating biological activities of a family of non-steroid hormone receptors, RARα/β/γ, and RXRα/β/γ. These DNA-binding transcription factors recognize DNA as RAR/RXR heterodimers and recruit multiprotein transcriptional co-repressor complexes. RA-binding to RAR receptors induces a conformational change in the receptor, followed by the replacement of co-repressor with co-activator complexes. Inactivation of RARα/β/γ receptors in the periocular mesenchyme abrogates anterior eye segment formation. This review summarizes recent genetic studies of RA signaling and progress in understanding the molecular mechanism of transcriptional co-activators that function with RAR/RXR.
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