Mendelsohn C, Ruberte E, LeMeur M, Morriss-Kay G, Chambon P
Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Institut de Chimie Biologique, Faculté de Médecine, Strasbourg, France.
Development. 1991 Nov;113(3):723-34. doi: 10.1242/dev.113.3.723.
Retinoic acid (RA) is a signalling molecule important for pattern formation during development. There are three known types of nuclear receptors for RA in mammals, RAR-alpha, RAR-beta and RAR-gamma, which transduce the RA signal by inducing or repressing the transcription of target genes. Here we describe the developmental expression pattern of the mouse RAR-beta 2 promoter. Independent lines of transgenic animals expressing RAR-beta 2 promoter sequences fused to the E. coli beta-galactosidase gene were examined throughout the course of embryogenesis and found to exhibit reproducible and specific patterns of beta-galactosidase expression in a majority of sites that have been shown previously to contain mRAR-beta transcripts. In the limbs, mRAR-beta 2 promoter activity and mRAR-beta transcripts were both excluded from precartilagenous condensations; interestingly, mRAR-beta 2 promoter activity was observed in the apical ectodermal ridge (AER) where mRAR-beta transcripts could not be detected, while no mRAR-beta 2 promoter activity or mRAR-beta transcripts were associated with the limb region that contains the zone of polarizing activity (ZPA). Analysis of the lacZ expression pattern in embryos from mothers treated with teratogenic doses of RA, indicated that mRAR-beta 2 promoter is selectively induced in a manner suggesting that overexpression of the mRAR-beta 2 isoform is involved in RA-generated malformations. The normal and induced expression pattern of the mRAR-beta 2 promoter suggests several possible roles for mRAR-beta 2 in development of the limbs, as an inhibitor of cartilage formation, in programmed cell death and in the formation of loose connective tissue.
视黄酸（RA）是一种在发育过程中对模式形成很重要的信号分子。在哺乳动物中，已知有三种RA核受体，即RAR-α、RAR-β和RAR-γ，它们通过诱导或抑制靶基因的转录来转导RA信号。在此，我们描述了小鼠RAR-β2启动子的发育表达模式。在整个胚胎发生过程中，对表达与大肠杆菌β-半乳糖苷酶基因融合的RAR-β2启动子序列的转基因动物独立品系进行了检测，发现在大多数先前已显示含有mRAR-β转录本的位点中，β-半乳糖苷酶表达呈现出可重复的特异性模式。在四肢中，mRAR-β2启动子活性和mRAR-β转录本均被排除在前软骨凝聚区之外；有趣的是，在无法检测到mRAR-β转录本的顶端外胚层嵴（AER）中观察到了mRAR-β2启动子活性，而在含有极化活性区（ZPA）的肢体区域未发现mRAR-β2启动子活性或mRAR-β转录本。对用致畸剂量的RA处理的母亲所生胚胎中lacZ表达模式的分析表明，mRAR-β2启动子以一种提示mRAR-β2异构体过表达参与RA诱导的畸形形成的方式被选择性诱导。mRAR-β2启动子的正常和诱导表达模式表明，mRAR-β2在四肢发育中可能具有多种作用，如作为软骨形成的抑制剂、参与程序性细胞死亡以及在疏松结缔组织形成中发挥作用。
