Cammas Laura, Romand Raymond, Fraulob Valérie, Mura Carole, Dollé Pascal
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Inserm, U596, CNRS, UMR 7104, Illkirch, France.
Dev Dyn. 2007 Oct;236(10):2899-908. doi: 10.1002/dvdy.21312.
Retinoic acid acts as a signalling molecule regulating many developmental events in vertebrates. As this molecule directly influences gene expression by activating nuclear receptors, its patterns of synthesis have to be tightly regulated, and it is well established that at least three retinaldehyde dehydrogenases (RALDHs) are involved in such tissue-specific synthesis. Whereas embryos from oviparous species can obtain retinaldehyde by metabolizing carotenoids stored in the yolk, placental embryos rely on retinol transferred from the maternal circulation. Here, we show that the gene encoding one of the murine retinol dehydrogenases, Rdh10, is expressed according to complex profiles both during early embryogenesis and organ differentiation. Many of its expression sites correlate with regions of active retinoid signalling and Raldh gene expression, especially with Raldh2 in the early presomitic and somitic mesoderm, retrocardiac and posterior branchial arch region, or later in the pleural mesothelium and kidney cortical region. Rdh10 also shows cell-type and/or regional specificity during development of the palate, teeth, and olfactory system. During limb bud development, it may participate in retinoic acid production in proximal/posterior cells, and eventually in interdigital mesenchyme. These data implicate the retinol to retinaldehyde conversion as the first step in the tissue-specific regulation of retinoic acid synthesis, at least in mammalian embryos.
视黄酸作为一种信号分子,调控脊椎动物许多发育过程。由于该分子通过激活核受体直接影响基因表达,其合成模式必须受到严格调控,并且已知至少三种视网膜醛脱氢酶(RALDHs)参与这种组织特异性合成。卵生动物的胚胎可通过代谢卵黄中储存的类胡萝卜素获得视网膜醛,而胎盘类胚胎则依赖于从母体循环中转移来的视黄醇。在此,我们表明,编码小鼠视黄醇脱氢酶之一Rdh10的基因,在早期胚胎发育和器官分化过程中均呈现复杂的表达模式。其许多表达位点与活跃的类视黄醇信号传导区域及Raldh基因表达区域相关,特别是在早期体节中胚层、体节、心后和后鳃弓区域与Raldh2相关,或在后期与胸膜间皮和肾皮质区域相关。在腭、牙齿和嗅觉系统发育过程中,Rdh10也表现出细胞类型和/或区域特异性。在肢芽发育过程中,它可能参与近端/后部细胞中视黄酸的产生,并最终参与指(趾)间充质中视黄酸的产生。这些数据表明,视黄醇向视网膜醛的转化是视黄酸合成组织特异性调控的第一步,至少在哺乳动物胚胎中是如此。