Lankenau Institute for Medical Research, 100 Lancaster Avenue, Wynnewood, PA 19096, USA.
Lankenau Institute for Medical Research, 100 Lancaster Avenue, Wynnewood, PA 19096, USA.
Dev Biol. 2011 Nov 1;359(1):12-25. doi: 10.1016/j.ydbio.2011.08.007. Epub 2011 Aug 18.
Cells that express MyoD mRNA, the G8 antigen and the bone morphogenetic protein (BMP) inhibitor noggin (Nog) are present in the epiblast before gastrulation. Ablation of "Myo/Nog" cells in the blastocyst results in an expansion of canonical BMP signaling and prevents the expression of noggin and follistatin before and after the onset of gastrulation. Once eliminated in the epiblast, they are neither replaced nor compensated for as development progresses. Older embryos lacking Myo/Nog cells exhibit severe axial malformations. Although Wnts and Sonic hedgehog are expressed in ablated embryos, skeletal muscle progenitors expressing Pax3 are missing in the somites. Pax3+ cells do emerge adjacent to Wnt3a+ cells in vitro; however, few undergo skeletal myogenesis. Ablation of Myo/Nog cells also results in ectopically placed cardiac progenitors and cardiomyocytes in the somites. Reintroduction of Myo/Nog cells into the epiblast of ablated embryos restores normal patterns of BMP signaling, morphogenesis and skeletal myogenesis, and inhibits the expression of cardiac markers in the somites. This study demonstrates that Myo/Nog cells are essential regulators of BMP signaling in the early epiblast and are indispensable for normal morphogenesis and striated muscle lineage specification.
在原肠胚形成之前，表达 MyoD mRNA、G8 抗原和骨形态发生蛋白（BMP）抑制剂 noggin（Nog）的细胞存在于上胚层中。在胚泡中剔除“Myo/Nog”细胞会导致经典 BMP 信号的扩张，并阻止 noggin 和 follistatin 在原肠胚形成前后的表达。一旦在上胚层中被消除，它们就不会被取代或补偿，因为发育会继续进行。缺乏 Myo/Nog 细胞的较老胚胎表现出严重的轴向畸形。尽管 Wnts 和 Sonic hedgehog 在被剔除的胚胎中表达，但在体节中缺乏表达 Pax3 的骨骼肌祖细胞。在体外，Pax3+细胞确实会出现在 Wnt3a+细胞附近；然而，很少有细胞经历骨骼肌发生。剔除 Myo/Nog 细胞也会导致心脏祖细胞和心肌细胞在体节中异位放置。将 Myo/Nog 细胞重新引入被剔除的胚胎的上胚层中，恢复了正常的 BMP 信号、形态发生和骨骼肌发生模式，并抑制了体节中心脏标志物的表达。这项研究表明，Myo/Nog 细胞是早期上胚层中 BMP 信号的重要调节剂，对于正常的形态发生和横纹肌谱系特化是不可或缺的。
