Two isoforms of Xenopus retinoic acid receptor gamma 2 (B) exhibit differential expression and sensitivity to retinoic acid during embryogenesis

Two isoforms of Xenopus retinoic acid receptor gamma 2 (B) exhibit differential expression and sensitivity to retinoic acid during embryogenesis
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DOI:
10.1002/dvg.1020170402
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发表时间:
1995-01-01
期刊:
DEVELOPMENTAL GENETICS
影响因子:
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通讯作者:
Varmuza, SL
Varmuza, SL
中科院分区:
其他
文献类型:
--
作者:
Crawford, MJ;Liversage, RA;Varmuza, SL

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我们报告的两个维甲酸受体亚型(RAR γ)的分离,不同之处仅在于5'非翻译和推定的N-末端A区。这两种亚型似乎作为推定的神经轴的早期标志物,然而,它们的表达模式不同。RAR-γ 2.1首先在背唇原肠胚形成时表达,随后沿着假定的神经轴表达。RAR-γ 2.2代表已经部分表征并作为母体转录物存在的受体cDNA的全长序列[Ellinger-Ziegelbauer和Dreyer(1991); Genes Dev 5:94-104,(1993):Mech Dev 41:31-46; Pfeffer和DeRobertis,(1994)Mech Dev:45:147-153]。与RAR-γ 2.2不同,2.1变体在前闪米特中胚层或脊索中均不表达。RAR-gamma 2.1在鳃弓中强烈表达,在神经底板中表达程度较小。这两种异构体对视黄酸也表现出不同的敏感性。视黄酸处理后,神经胚形成后RAR-γ 2.2的组成型表达似乎受到抑制,但最高表达的区域,即头部和尾部,保持相对不受影响,晚期神经胚形成前的表达模式也是如此。相比之下,RAR-γ 2.1在类维生素A抑制的结构中不转录。使用显微注射技术,我们表明,RAR-γ 2.1的表达在假定的头部结构的变化发生作为维甲酸管理的早期和局部的后果。由于视黄酸抑制RAR-γ 2.1的表达,我们测试了其他干扰轴形成的治疗是否有任何影响。令人惊讶的是,紫外线照射并没有抑制RAR-γ 2.1转录本的表达,这表明视黄酸的抑制作用不仅仅是由于抑制了前神经发育。这些实验证明了一种新的亚型,在发展过程中经历差异表达,并表现出不同的敏感性视黄酸和紫外线。这种敏感性和这种亚型变体在已知表现出极化活性的区域中的存在加强了这些受体在形态发生期间起主要作用的假设。(C)1995 Wiley-Liss,Inc.
We report the isolation of two retinoic acid receptor isoforms (RAR gamma), which differ only in the 5' untranslated and putative N-terminus A regions. The two isoforms appear to serve as early markers for the presumptive neural axis; however, their expression patterns differ. RAR-gamma 2.1 is first expressed at gastrulation at the dorsal lip and subsequently along the presumptive neural axis. RAR-gamma 2.2 represents the full-length sequence of a receptor cDNA already partially characterized and present as a maternal transcript [Ellinger-Ziegelbauer and Dreyer (1991); Genes Dev 5:94-104, (1993): Mech Dev 41:31-46; Pfeffer and DeRobertis, (1994) Mech Dev: 45:147-153]. Unlike RAR-gamma 2.2, the 2.1 variant is not expressed either in pre-semitic mesoderm or notochord. RAR-gamma 2.1 is strongly expressed in branchial arches and to a lesser extent in the neural floor plate. The two isoforms also exhibit differential sensitivity to retinoic acid. Constitutive expression of RAR-gamma 2.2 following neurulation appears to be depressed by treatment with retinoic acid, but domains of highest expression, namely, the head and tail, remain relatively unaffected, as do patterns of expression prior to late neurulation. By contrast, RAR-gamma 2.1 is not transcribed in retinoid-inhibited structures. Using microinjection techniques, we show that changes of RAR-gamma 2.1 expression in presumptive head structures occur as an early and local consequence of retinoic acid administration. Since RAR-gamma 2.1 expression is inhibited by retinoic acid, we tested to see if other treatments that perturb axis formation had any effect. Surprisingly, UV irradiation did not suppress expression of the RAR-gamma 2.1 transcript, suggesting that its inhibition by retinoic acid is not due solely to inhibition of anterior neural development. These experiments demonstrate a new subdivision of isoforms that undergo differential expression during development and that exhibit differential sensitivity to retinoic acid and to UV. This sensitivity and the presence of this isoform variant in regions that are known to exhibit polarizing activity strengthen the hypothesis that these receptors play a primary role during morphogenesis. (C) 1995 Wiley-Liss, Inc.