Cheng T C, Hanley T A, Mudd J, Merlie J P, Olson E N
Department of Biochemistry and Molecular Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
J Cell Biol. 1992 Dec;119(6):1649-56. doi: 10.1083/jcb.119.6.1649.
During vertebrate embryogenesis, the muscle-specific helix-loop-helix protein myogenin is expressed in muscle cell precursors in the developing somite myotome and limb bud before muscle fiber formation and is further upregulated during myogenesis. We show that cis-acting DNA sequences within the 5' flanking region of the mouse myogenin gene are sufficient to direct appropriate temporal, spatial, and tissue-specific transcription of myogenin during mouse embryogenesis. Myogenin-lacZ transgenes trace the fate of embryonic cells that activate myogenin transcription and suggest that myogenic precursor cells that migrate from the somite myotome to the limb bud are committed to a myogenic fate in the absence of myogenin transcription. Activation of a myogenin-lacZ transgene can occur in limb bud explants in culture, indicating that signals required for activation of myogenin transcription are intrinsic to the limb bud and independent of other parts of the embryo. These results reveal multiple populations of myogenic precursor cells during development and suggest the existence of regulators other than myogenic helix-loop-helix proteins that maintain cells in the early limb bud in the myogenic lineage.
在脊椎动物胚胎发育过程中，肌肉特异性螺旋-环-螺旋蛋白肌细胞生成素在发育中的体节肌节和肢芽的肌肉细胞前体中表达，先于肌纤维形成，且在肌生成过程中进一步上调。我们发现，小鼠肌细胞生成素基因5'侧翼区域内的顺式作用DNA序列足以在小鼠胚胎发育过程中指导肌细胞生成素进行适当的时间、空间和组织特异性转录。肌细胞生成素-乳糖操纵子转基因追踪激活肌细胞生成素转录的胚胎细胞的命运，并表明从体节肌节迁移到肢芽的生肌前体细胞在没有肌细胞生成素转录的情况下就已确定为生肌命运。肌细胞生成素-乳糖操纵子转基因在培养的肢芽外植体中能够被激活，这表明激活肌细胞生成素转录所需的信号是肢芽所固有的，且独立于胚胎的其他部分。这些结果揭示了发育过程中生肌前体细胞的多个群体，并表明除了生肌螺旋-环-螺旋蛋白之外，还存在其他调节因子，这些因子可使早期肢芽中的细胞维持在生肌谱系中。
