Manceau Marie, Gros Jérôme, Savage Kathleen, Thomé Virginie, McPherron Alexandra, Paterson Bruce, Marcelle Christophe
Developmental Biology Institute of Marseille Luminy, CNRS UMR 6216, Université de la Méditerranée, Campus de Luminy, 13288 Marseille Cedex 09, France.
Genes Dev. 2008 Mar 1;22(5):668-81. doi: 10.1101/gad.454408.
Myostatin, a TGF-beta family member, is an important regulator of adult muscle size. While extensively studied in vitro, the mechanisms by which this molecule mediates its effect in vivo are poorly understood. We addressed this question using chick and mouse embryos. We show that while myostatin overexpression in chick leads to an exhaustion of the muscle progenitor population that ultimately results in muscle hypotrophy, myostatin loss of function in chick and mouse provokes an expansion of this population. Our data demonstrate that myostatin acts in vivo to regulate the balance between proliferation and differentiation of embryonic muscle progenitors by promoting their terminal differentiation through the activation of p21 and MyoD. Previous studies have suggested that myostatin imposes quiescence on muscle progenitors. Our data suggest that myostatin's effect on muscle progenitors is more complex than previously realized and is likely to be context-dependent. We propose a novel model for myostatin mode of action in vivo, in which myostatin affects the balance between proliferation and differentiation of embryonic muscle progenitors by enhancing their differentiation.
肌肉生长抑制素是转化生长因子-β（TGF-β）家族的成员，是成年肌肉大小的重要调节因子。虽然在体外进行了广泛研究，但对该分子在体内介导其作用的机制了解甚少。我们利用鸡和小鼠胚胎解决了这个问题。我们发现，虽然在鸡中过表达肌肉生长抑制素会导致肌肉祖细胞群体耗尽，最终导致肌肉萎缩，但在鸡和小鼠中肌肉生长抑制素功能丧失会促使该群体扩张。我们的数据表明，肌肉生长抑制素在体内通过激活p21和MyoD促进胚胎肌肉祖细胞的终末分化，从而调节其增殖与分化之间的平衡。先前的研究表明，肌肉生长抑制素使肌肉祖细胞进入静止状态。我们的数据表明，肌肉生长抑制素对肌肉祖细胞的影响比之前认识到的更为复杂，可能取决于具体情况。我们提出了一个肌肉生长抑制素在体内作用模式的新模型，其中肌肉生长抑制素通过增强胚胎肌肉祖细胞的分化来影响其增殖与分化之间的平衡。
