Delfini M C, Hirsinger E, Pourquié O, Duprez D
Institut d'Embryologie Cellulaire et Moléculaire du CNRS (FRE2160) et du Collège de France, 94736 Nogent sur Marne Cedex, France.
Development. 2000 Dec;127(23):5213-24. doi: 10.1242/dev.127.23.5213.
The myogenic basic helix-loop-helix (bHLH) transcription factors, Myf5, MyoD, myogenin and MRF4, are unique in their ability to direct a program of specific gene transcription leading to skeletal muscle phenotype. The observation that Myf5 and MyoD can force myogenic conversion in non-muscle cells in vitro does not imply that they are equivalent. In this paper, we show that Myf5 transcripts are detected before those of MyoD during chick limb development. The Myf5 expression domain resembles that of Pax3 and is larger than that of MyoD. Moreover, Myf5 and Pax3 expression is correlated with myoblast proliferation, while MyoD is detected in post-mitotic myoblasts. These data indicate that Myf5 and MyoD are involved in different steps during chick limb bud myogenesis, Myf5 acting upstream of MyoD. The progression of myoblasts through the differentiation steps must be carefully controlled to ensure myogenesis at the right place and time during wing development. Because Notch signalling is known to prevent differentiation in different systems and species, we sought to determine whether these molecules regulate the steps occurring during chick limb myogenesis. Notch1 transcripts are associated with immature myoblasts, while cells expressing the ligands Delta1 and Serrate2 are more advanced in myogenesis. Misexpression of Delta1 using a replication-competent retrovirus activates the Notch pathway. After activation of this pathway, myoblasts still express Myf5 and Pax3 but have downregulated MyoD, resulting in inhibition of terminal muscle differentiation. We conclude that activation of Notch signalling during chick limb myogenesis prevents Myf5-expressing myoblasts from progressing to the MyoD-expressing stage.
生肌碱性螺旋-环-螺旋（bHLH）转录因子Myf5、MyoD、肌细胞生成素和成肌调节因子4（MRF4）在指导特定基因转录程序从而导致骨骼肌表型形成的能力方面独具特色。Myf5和MyoD能在体外促使非肌肉细胞发生生肌转化这一观察结果并不意味着它们是等同的。在本文中，我们发现在鸡胚肢体发育过程中，Myf5转录本比MyoD的转录本更早被检测到。Myf5的表达域与Pax3的相似，且比MyoD的更大。此外，Myf5和Pax3的表达与成肌细胞增殖相关，而MyoD在有丝分裂后的成肌细胞中被检测到。这些数据表明，Myf5和MyoD在鸡胚肢体芽生肌过程中参与不同步骤，Myf5在MyoD的上游起作用。成肌细胞通过分化步骤的进程必须得到严格控制，以确保在翅膀发育的正确位置和时间发生生肌作用。由于已知Notch信号通路在不同系统和物种中会阻止分化，我们试图确定这些分子是否调节鸡胚肢体生肌过程中发生的步骤。Notch1转录本与未成熟的成肌细胞相关，而表达配体Delta1和锯齿蛋白2的细胞在生肌过程中更为成熟。使用具有复制能力的逆转录病毒错表达Delta1会激活Notch信号通路。该信号通路激活后，成肌细胞仍表达Myf5和Pax3，但下调了MyoD的表达，从而导致终末肌肉分化受到抑制。我们得出结论，在鸡胚肢体生肌过程中Notch信号通路的激活会阻止表达Myf5的成肌细胞进入表达MyoD的阶段。
