The regulation and action of myostatin as a negative regulator of muscle development during avian embryogenesis
The regulation and action of myostatin as a negative regulator of muscle development during avian embryogenesis
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DOI：
10.1006/dbio.2002.0812
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发表时间：
2002-11-15
影响因子：
2.7
通讯作者：
Patel, K
中科院分区：
文献类型：
--
作者：
Amthor, H;Huang, RJ;Patel, K
肌肉生长抑制素是一种强有力的肌肉生长抑制因子。Myostatin基因缺失会导致骨骼肌大量增生和肥大。然而，整体肌肉图案被保留下来。我们发现，在鸡胚胎发育过程中，肌肉抑制素在不太可能影响肌肉质量发育的阶段和位置表达。在体节中，Myostatin主要在皮肌节的中央区域表达，而不是在背内侧和腹外侧唇表达，那里是肌肉伸长的大部分细胞。在肢芽发育过程中，Myostatin在早期阶段在肌源性和非肌源性区域都瞬时表达。肌肉抑制素在肢芽发育过程中重新表达，此时肌肉正在分裂。异位发育的不能形成肌肉的翼芽仍然表达肌肉抑制素。这表明，在肢体中，并不是所有的Myostatin表达细胞都是肌源性细胞。外胚层和声学刺猬对Myostatin的表达有不同的影响，这取决于手术的分期和术后的时间长度。最后，我们发现，在发育中的肢芽中应用Myostatin蛋白会导致Pax-3和Myf-5基因的下调，这两个基因都与肌源性细胞的增殖有关；此外，Myostatin还可以阻止MyoD的表达，MyoD是一个与肌肉分化相关的基因。肌肉抑制素治疗的长期效果会导致四肢肌肉的不足。因此，Myostatin对转录因子的基因表达产生负面影响，而转录因子是建立肌源性细胞特性所必需的。(C)2002年爱思唯尔科学公司(美国)
Myostatin is a potent inhibitor of muscle growth. Genetic deletion of Myostatin leads to massive hyperplasia and hypertrophy of skeletal muscle. However, the overall muscle pattern is preserved. We show that, during chick embryonic development, Myostatin is expressed at stages and positions unlikely to influence qualitative muscle development. In the somites, Myostatin is predominantly expressed in a central domain of the dermomyotome but not at the dorsomedial and ventrolateral lips, where most cells for myotomal elongation are recruited. During limb bud development, Myostatin is transiently expressed at early stages in both myogenic and nonmyogenic regions. Myostatin is reexpressed during limb bud development at a time when splitting of muscle is underway. Heterotopically developed wing buds that fail to form muscle still express Myostatin. This demonstrates that, in the limb, not all Myostatin-expressing cells are of myogenic origin. Ectoderm and Sonic hedgehog have different effects on the expression of Myostatin dependent on stages at which the operation was performed and the length of the postoperative period. Finally, we show that application of Myostatin protein into the developing limb bud results in a down-regulation of Pax-3 and Myf-5, both genes associated with proliferation of myogenic cells; and, furthermore, Myostatin also prevents the expression of MyoD, a gene associated with muscle differentiation. The long-term effect of Myostatin treatment leads to a deficiency of limb muscle. Therefore, Myostatin negatively affects gene expression of transcription factors, which are necessary for establishing myogenic cell identity. (C) 2002 Elsevier Science (USA)