Key roles of retinoic acid receptors alpha and beta in the patterning of the caudal hindbrain, pharyngeal arches and otocyst in the mouse.
Key roles of retinoic acid receptors alpha and beta in the patterning of the caudal hindbrain, pharyngeal arches and otocyst in the mouse.
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发表时间：
1999-11
期刊：
影响因子：
4.6
通讯作者：
V. Dupé;N. Ghyselinck;O. Wendling;P. Chambon;M. Mark
中科院分区：
文献类型：
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作者：
V. Dupé;N. Ghyselinck;O. Wendling;P. Chambon;M. Mark
携带RAR（β）和RAR β基因的靶向失活的小鼠胎儿在已知部分来源于源自耳后菱形体（例如胸腺和头大动脉）的间充质神经嵴的结构中显示出多种畸形（Ghyselinck，N.，Dupé，V.，Dierich，A.，Messaddeq，N.，Garnier，J.M.，Rochette-Egly，C.，Chambon，P.和Mark M.（1997年）。Int. J. Dev. 41，425-447）。在寻找神经嵴缺陷，我们已经分析了菱形，颅神经和咽弓的这些双无效突变体在早期胚胎阶段。突变的耳后颅神经是紊乱的，表明RAR参与了神经源性神经嵴衍生的结构的模式化，即使缺乏RAR α和RAR β对神经嵴细胞的数量和迁移路径没有可检测的影响。有趣的是，双无效突变损害了已知独立于神经嵴的早期发育过程，第3、4鳃囊和第3、4、6弓动脉的初步形成。双突变也导致扩大的菱形5，这是可能是负责的诱导额外的耳泡，在一个消失的菱形5/6边界，并在深刻的改变菱形身份。在突变的后脑中，kreisler的表达域是其正常大小的两倍，并且Krox-20的尾侧条纹延伸到假定的菱形节6和7区域。在该区域，Hoxb-1异位表达，Hoxb-3异位上调，Hoxd-4表达被消除。这些数据，这表明视黄酸信号通过RAR α和/或RAR β是必不可少的规范的菱形体的身份和控制尾部后脑分割通过限制的表达结构域的kreisler和Krox-20，也强烈表明，这种信号在后脑神经外胚层的posteriorization起着至关重要的作用。
Mouse fetuses carrying targeted inactivations of both the RAR() and the RARbeta genes display a variety of malformations in structures known to be partially derived from the mesenchymal neural crest originating from post-otic rhombomeres (e.g. thymus and great cephalic arteries) (Ghyselinck, N., Dupé, V., Dierich, A., Messaddeq, N., Garnier, J.M., Rochette-Egly, C., Chambon, P. and Mark M. (1997). Int. J. Dev. Biol. 41, 425-447). In a search for neural crest defects, we have analysed the rhombomeres, cranial nerves and pharyngeal arches of these double null mutants at early embryonic stages. The mutant post-otic cranial nerves are disorganized, indicating that RARs are involved in the patterning of structures derived from neurogenic neural crest, even though the lack of RARalpha and RARbeta has no detectable effect on the number and migration path of neural crest cells. Interestingly, the double null mutation impairs early developmental processes known to be independent of the neural crest e.g., the initial formation of the 3rd and 4th branchial pouches and of the 3rd, 4th and 6th arch arteries. The double mutation also results in an enlargement of rhombomere 5, which is likely to be responsible for the induction of supernumerary otic vesicles, in a disappearance of the rhombomere 5/6 boundary, and in profound alterations of rhombomere identities. In the mutant hindbrain, the expression domain of kreisler is twice its normal size and the caudal stripe of Krox-20 extends into the presumptive rhombomeres 6 and 7 region. In this region, Hoxb-1 is ectopically expressed, Hoxb-3 is ectopically up-regulated and Hoxd-4 expression is abolished. These data, which indicate that retinoic acid signaling through RARalpha and/or RARbeta is essential for the specification of rhombomere identities and for the control of caudal hindbrain segmentation by restricting the expression domains of kreisler and of Krox-20, also strongly suggest that this signaling plays a crucial role in the posteriorization of the hindbrain neurectoderm.