Myo/Nog cell regulation of bone morphogenetic protein signaling in the blastocyst is essential for normal morphogenesis and striated muscle lineage specification.

Myo/Nog cell regulation of bone morphogenetic protein signaling in the blastocyst is essential for normal morphogenesis and striated muscle lineage specification.
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DOI:
10.1016/j.ydbio.2011.08.007
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发表时间:
2011-11-01
影响因子:
2.7
通讯作者:
George-Weinstein M
George-Weinstein M
中科院分区:
生物学3区
文献类型:
--
作者:
Gerhart J;Scheinfeld VL;Milito T;Pfautz J;Neely C;Fisher-Vance D;Sutter K;Crawford M;Knudsen K;George-Weinstein M

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原肠胚形成前外胚层中存在表达MyoD mRNA、G8抗原和骨形态发生蛋白(BMP)抑制剂noggin (Nog)的细胞。囊胚中“Myo/Nog”细胞的消融导致典型BMP信号的扩增,并在原肠形成开始前后阻止noggin和卵泡抑素的表达。一旦在外胚层中被消灭,随着发育的进展,它们既不能被取代,也不能得到补偿。缺少Myo/Nog细胞的老年胚胎表现出严重的轴向畸形。虽然wnt和Sonic hedgehog基因在消融胚胎中表达,但在体细胞中缺失表达Pax3的骨骼肌祖细胞。Pax3+细胞确实在体外与Wnt3a+细胞相邻出现;然而,很少发生骨骼肌发生。Myo/Nog细胞的消融也会导致心脏祖细胞和体细胞中的心肌细胞异位。将Myo/Nog细胞重新引入消融胚胎的外胚层可恢复BMP信号、形态发生和骨骼肌发生的正常模式,并抑制体中心脏标志物的表达。该研究表明,Myo/Nog细胞是早期外胚层BMP信号的重要调节因子,对正常形态发生和横纹肌谱系的形成是必不可少的。
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.
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