Developmental expression of retinoic acid receptors (RARs).

Developmental expression of retinoic acid receptors (RARs).
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DOI:
10.1621/nrs.07006
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发表时间:
2009-05-12
期刊:
Nuclear receptor signaling
影响因子:
--
通讯作者:
Dollé P
Dollé P
中科院分区:
其他
文献类型:
--
作者:
Dollé P

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在这里,我回顾了维甲酸受体(RARs)和“维甲酸X”或rexinoid受体(RXRs)编码基因的发育表达特征。第一个详细的表达研究是在二十多年前在小鼠中进行的,随后克隆了小鼠Rar基因。这些研究揭示了在植入后发育的所有阶段的复杂表达特征,一个受体基因(Rara)显示广泛表达,另外两个(Rarb和Rarg)在神经和非神经组织中具有高度区域化和/或细胞类型特异性表达。Rxr基因也具有广泛的(Rxra,Rxrb)或高度限制的(Rxrg)表达模式。在斑马鱼和非洲爪蟾中进行的研究表明,在早期原肠胚形成前阶段,Rar和Rxr基因(母体和合子)都有表达。参与视黄酸合成的特定酶(视黄醇/视黄醇醛脱氢酶)的最终表征,或其催化剂的触发(CYP 26细胞色素P450),所有这些都显示出差异表达模式,导致更清楚地了解发育过程中视黄酸信号调节的现象。涉及小鼠靶向基因破坏的功能研究,以及其他模型中的显性负性受体表达等其他方法,已经确定了RAR和RXR在许多发育器官系统中的特定(而不是部分冗余)作用。这些多效性作用在下文中与受体表达模式的关系进行了总结。
Here, I review the developmental expression features of genes encoding the retinoic acid receptors (RARs) and the 'retinoid X' or rexinoid receptors (RXRs). The first detailed expression studies were performed in the mouse over two decades ago, following the cloning of the murine Rar genes. These studies revealed complex expression features at all stages of post-implantation development, one receptor gene (Rara) showing widespread expression, the two others (Rarb and Rarg) with highly regionalized and/or cell type-specific expression in both neural and non-neural tissues. Rxr genes also have either widespread (Rxra, Rxrb), or highly-restricted (Rxrg) expression patterns. Studies performed in zebrafish and Xenopus demonstrated expression of Rar and Rxr genes (both maternal and zygotic), at early pre-gastrulation stages. The eventual characterization of specific enzymes involved in the synthesis of retinoic acid (retinol/retinaldehyde dehydrogenases), or the triggering of its catabolism (CYP26 cytochrome P450s), all of them showing differential expression patterns, led to a clearer understanding of the phenomenons regulated by retinoic acid signaling during development. Functional studies involving targeted gene disruptions in the mouse, and additional approaches such as dominant negative receptor expression in other models, have pinpointed the specific, versus partly redundant, roles of the RARs and RXRs in many developing organ systems. These pleiotropic roles are summarized hereafter in relationship to the receptors’ expression patterns.