Hutcheson David A, Zhao Jia, Merrell Allyson, Haldar Malay, Kardon Gabrielle
Department of Human Genetics, University of Utah, Salt Lake City, Utah 84112, USA.
Genes Dev. 2009 Apr 15;23(8):997-1013. doi: 10.1101/gad.1769009. Epub 2009 Apr 3.
Vertebrate muscle arises sequentially from embryonic, fetal, and adult myoblasts. Although functionally distinct, it is unclear whether these myoblast classes develop from common or different progenitors. Pax3 and Pax7 are expressed by somitic myogenic progenitors and are critical myogenic determinants. To test the developmental origin of embryonic and fetal myogenic cells in the limb, we genetically labeled and ablated Pax3(+) and Pax7(+) cells. Pax3(+)Pax7(-) cells contribute to muscle and endothelium, establish and are required for embryonic myogenesis, and give rise to Pax7(+) cells. Subsequently, Pax7(+) cells give rise to and are required for fetal myogenesis. Thus, Pax3(+) and Pax7(+) cells contribute differentially to embryonic and fetal limb myogenesis. To investigate whether embryonic and fetal limb myogenic cells have different genetic requirements we conditionally inactivated or activated beta-catenin, an important regulator of myogenesis, in Pax3- or Pax7-derived cells. beta-Catenin is necessary within the somite for dermomyotome and myotome formation and delamination of limb myogenic progenitors. In the limb, beta-catenin is not required for embryonic myoblast specification or myofiber differentiation but is critical for determining fetal progenitor number and myofiber number and type. Together, these studies demonstrate that limb embryonic and fetal myogenic cells develop from distinct, but related progenitors and have different cell-autonomous requirements for beta-catenin.
脊椎动物的肌肉依次由胚胎、胎儿和成体肌母细胞产生。尽管功能不同，但尚不清楚这些肌母细胞类别是由共同的还是不同的祖细胞发育而来。Pax3和Pax7由体节生肌祖细胞表达，是关键的生肌决定因素。为了测试肢体中胚胎和成体生肌细胞的发育起源，我们对Pax3(+)和Pax7(+)细胞进行了基因标记和消融。Pax3(+)Pax7(-)细胞对肌肉和内皮有贡献，建立胚胎肌生成并为之所必需，还产生Pax7(+)细胞。随后，Pax7(+)细胞产生胎儿肌生成并为之所必需。因此，Pax3(+)和Pax7(+)细胞对胚胎和胎儿肢体肌生成的贡献不同。为了研究胚胎和胎儿肢体生肌细胞是否有不同的基因需求，我们在源自Pax3或Pax7的细胞中条件性地失活或激活β-连环蛋白，它是生肌的重要调节因子。β-连环蛋白在体节内对于皮肌节、肌节的形成以及肢体生肌祖细胞的分层是必需的。在肢体中，β-连环蛋白对于胚胎肌母细胞的特化或肌纤维分化不是必需的，但对于确定胎儿祖细胞数量以及肌纤维数量和类型至关重要。总之，这些研究表明肢体胚胎和胎儿生肌细胞由不同但相关的祖细胞发育而来，并且对β-连环蛋白有不同的细胞自主需求。
