Regulation of a muscle-specific transgene by retinoic acid.
Regulation of a muscle-specific transgene by retinoic acid.
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DOI：
10.1083/jcb.129.5.1345
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发表时间：
1995-06
期刊：
影响因子：
--
通讯作者：
Rosenthal N
中科院分区：
文献类型：
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作者：
Xiao Y;Grieshammer U;Rosenthal N
视黄酸（RA）已被证明对细胞培养中的肌原性分化具有不同的影响。 RA 在胚胎体节、肢芽和新生儿肢体的原代培养物上的应用以剂量依赖性方式抑制肌原性分化，如抑制以下各项所示：(a) 肌管形成，(b) 肌球蛋白重链蛋白积累，(c) 肌球蛋白轻链 (MLC) 1/3、α sk-肌动蛋白和肌原性因子转录物表达。视黄酸受体（RAR）的表达也受到 RA 治疗的影响，特别是 RAR γ 转录物被诱导。为了进一步了解 RA 对肌生成的多效性作用，我们利用了两个肌肉特异性转基因标记，它们由 CAT 报告基因组成，由来自肌球蛋白轻链 1/3 位点 (MLC-CAT) 或 α-骨骼肌动蛋白基因 (α sk 肌动蛋白-CAT) 的调控元件驱动。 RA 抑制 MLC-CAT 转基因，但不抑制这些小鼠原代培养物中的 αsk 肌动蛋白-CAT 转基因表达。对转基因小鼠原代培养物和稳定转染的 C2C12 细胞中 MLC-CAT 表达的分析表明，RA 对 MLC-CAT 活性的抑制依赖于鸡胚提取物中的扩散因子。我们假设在发育过程中，RA对肌发生的多效性不仅仅取决于RA本身的分布和浓度，还受到胚胎环境中细胞外信号的影响。
Retinoic acid (RA) has been shown to have variable effects on myogenic differentiation in cell culture. The application of RA on primary cultures of embryonic somites, limb buds, and neonatal limbs inhibited myogenic differentiation in a dose-dependent way as indicated by the repression of: (a) myotube formation, (b) myosin heavy chain protein accumulation, (c) myosin light chain (MLC) 1/3, alpha sk-actin and myogenic factor transcript expression. Expression of retinoic acid receptors (RAR) was also affected by RA treatment, specifically RAR gamma transcripts were induced. To further understand the pleiotropic action of RA on myogenesis, we took advantage of two muscle-specific transgene markers which consisted of CAT reporter genes driven by regulatory elements either from the myosin light chain 1/3 locus (MLC- CAT) or the alpha-skeletal actin gene (alpha sk actin-CAT). RA inhibited MLC-CAT transgene but not alpha sk actin-CAT transgene expression in primary cultures from these mice. Analysis of MLC-CAT expression in transgenic mouse primary cultures and in stably transfected C2C12 cells demonstrated that repression of MLC-CAT activity by RA was dependent upon diffusible factors in chick embryo extract. We hypothesize that during development, the pleiotropic effects of RA on myogenesis do not depend solely on the distribution and concentration of RA itself, but are also influenced by extracellular signals in the embryonic environment.