Yamane A, Takahashi K, Mayo M, Vo H, Shum L, Zeichner-David M, Slavkin H C
Department of Pharmacology, School of Dental Medicine, Tsurumi University, Yokohama, Japan.
Arch Oral Biol. 1998 May;43(5):407-16. doi: 10.1016/s0003-9969(98)00018-1.
Significant progress has been made in defining mechanisms governing myogenesis at the transcriptional levels, but the extracellular signal-transduction pathways involved in myogenesis are not as yet defined. The developing mouse tongue provides a model for the regulation of myogenesis during precise time periods in embryogenesis. The molecular cues that regulate the close-range autocrine and/or paracrine signalling processes required for the fast-twitch complex tongue musculature are not known. This study was designed to test the hypothesis that transforming growth factor-alpha (TGF alpha) controls myogenesis in embryonic mouse tongue through the induction of myogenic regulatory factors such as myoD, myf5, myogenin and MRF4/myf6/herculin. To test this hypothesis, the effects of exogenous TGF alpha on the transcription of myoD, myf5, myogenin, MRF4 and desmin were examined in tongue samples from embryonic day-10.5 mandibular explants cultured in serum-free, chemically defined medium and then processed for competitive, reverse transcription-polymerase chain reaction. TGF alpha induced myoD, myogenin and desmin expression. Treatment with 20 and 40 ng/ml TGF alpha decreased or downregulated myf5 mRNA. MRF4 was not detected in the explants. TGF alpha apparently induces the early developmental stages of myogenesis through sequential upregulation of myoD and myogenin, downregulation of myf5 and corresponding significant increases in muscle-specific gene expression such as desmin transcription.
在确定转录水平上控制肌生成的机制方面已取得重大进展，但参与肌生成的细胞外信号转导途径尚未明确。发育中的小鼠舌头为胚胎发育特定时间段内肌生成的调控提供了一个模型。调节快肌复合舌肌所需的近距离自分泌和/或旁分泌信号传导过程的分子线索尚不清楚。本研究旨在验证转化生长因子-α（TGFα）通过诱导肌生成调节因子如肌分化抗原（MyoD）、肌原性决定因子5（Myf5）、肌细胞生成素（Myogenin）和MRF4/肌原性因子6（Myf6）/赫库林（Herculin）来控制胚胎小鼠舌头肌生成的假说。为验证这一假说，在无血清、化学成分明确的培养基中培养的胚胎第10.5天下颌外植体的舌头样本中，检测外源性TGFα对MyoD、Myf5、Myogenin、MRF4和结蛋白转录的影响，然后进行竞争性逆转录-聚合酶链反应。TGFα诱导MyoD、Myogenin和结蛋白表达。用20和40 ng/ml TGFα处理可降低或下调Myf5 mRNA。在外植体中未检测到MRF4。TGFα显然通过依次上调MyoD和Myogenin、下调Myf5以及相应显著增加肌肉特异性基因表达如结蛋白转录，诱导肌生成的早期发育阶段。
