Impairing retinoic acid signalling in the neural crest cells is sufficient to alter entire eye morphogenesis
Impairing retinoic acid signalling in the neural crest cells is sufficient to alter entire eye morphogenesis
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DOI：
10.1016/j.ydbio.2008.04.039
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发表时间：
2008-08-01
影响因子：
2.7
通讯作者：
Dupe, Valerie
中科院分区：
文献类型：
--
作者：
Matt, Nicolas;Ghyselinck, Norbert B.;Dupe, Valerie
已知视黄酸（RA）通过视黄酸受体（RAR）在不同水平的眼部图案中是必需的；然而，这些核受体触发的分子和细胞机制仍然不清楚。这里进行的遗传学研究使美国能够提出一种新模型来研究眼睛发育过程中 RA 的作用。通过灭活三种 RAR，特别是在眼周间充质中，我们区分了每种 RAR 在眼睛发育过程中的个体贡献，并描述了 RAR 在视神经形成过程中的新功能。我们证明 RAR α 是在眼发育过程中神经外胚层中介导 RA 信号传导的唯一受体。令人惊讶的是，尽管发育中的视网膜中存在复杂的 RA 活性模式，但我们观察到 RA 信号传导并不是眼睛形成的组织中自主需要的。我们发现 RA 在眼睛形态发生过程中的作用专门发生在神经嵴衍生的眼周间充质中，并且由所有三种 RAR 介导。此外，我们指出，编码同源域转录因子的 Pitx2 是眼睛发育过程中神经嵴细胞中关键的 RA 反应基因。有趣的是，我们观察到神经嵴细胞中的 RA 是眼外肌正常位置所必需的。 (C) 2008 Elsevier Inc. 保留所有权利。
Retinoic acid (RA) is known to be required at various levels of eye patterning via Retinoic Acid Receptors (RAR); however the molecular and cellular mechanisms triggered by these nuclear receptors are still obscure. The genetic studies performed here enable US to present a new model to study RA action during eye development. By inactivating the three RARs, specifically in the periocular mesenchyme, we discriminate the individual contribution of each RAR during eye development and describe a new function for RARs during the formation of the optic nerve. We demonstrate that RAR alpha is the only receptor that mediates RA signalling in the neurectoderm during ocular development. Surprisingly, and despite a sophisticated pattern of RA-activity in the developing retina, we observed that RA signalling is not autonomously required in this tissue for eye Formation. We show that the action of RA during eye morphogenesis is occurring specifically in neural crest-derived periocular mesenchyme and is mediated by all three RARs. Furthermore, we point out that Pitx2, which encodes a homeodomain transcription factor, is a key RA-responsive gene in neural crest cells during eye development. Interestingly, we observed that RA is required in the neural Crest cells for normal position of the extraocular muscle. (C) 2008 Elsevier Inc. All rights reserved.