MyoD-expressing progenitors are essential for skeletal myogenesis and satellite cell development.
MyoD-expressing progenitors are essential for skeletal myogenesis and satellite cell development.
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DOI：
10.1016/j.ydbio.2013.09.012
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发表时间：
2013-12-01
影响因子：
2.7
通讯作者：
Goldhamer, David J.
中科院分区：
文献类型：
--
作者：
Wood, William M.;Etemad, Shervin;Yamamoto, Masakazu;Goldhamer, David J.
关键词：
胚胎中的骨骼肌生成受到肌肉调节因子 (MRF) MyoD 家族协调表达的调节。 MyoD 和 Myf-5 是主要的肌肉谱系决定因子，以部分冗余的方式发挥作用来建立肌肉祖细胞身份。先前的白喉毒素（DTA）介导的消融研究表明，MyoD+祖细胞可以挽救胚胎中的肌生成，其中表达Myf-5的细胞被靶向消融，这提高了不同的MRF表达群体的调节行为解释这些MRF的功能补偿活动的可能性。使用 MyoDiCre 小鼠，通过肌球蛋白重链 (MyHC) 和肌细胞生成素染色检测，DTA 介导的 MyoD 表达细胞消融导致胚胎 12.5 天 (E12.5) 肌生成停止。重要的是，MyoDiCre/+；R26DTA/+ 胚胎表现出 Myf-5+ 祖细胞的伴随损失，表明绝大多数 Myf-5+ 祖细胞表达 MyoD，这一结论与 MyoDiCre 谱系标记胚胎中 Myf-5 蛋白表达的免疫荧光分析一致。令人惊讶的是，配对盒转录因子 Pax7 的染色也被 E12.5 丢失，Pax7 在躯干中的 MyoD 基因上游发挥作用，是胎儿成肌细胞和卫星细胞祖细胞的标记。 ACTA1Cre;R26DTA/+ 胚胎中分化骨骼肌的特异性消融对 MyoD+、Myf-5+ 和 Pax7+ 祖细胞产生相对较小的影响，表明细胞非自主效应不太可能解释 MyoDiCre/+;R26DTA/+ 胚胎中肌源性祖细胞的快速丧失。我们得出的结论是，绝大多数生肌群体都会经历 MyoD+ 状态，并且 MyoD+ 祖细胞对于肌发生和干细胞发育至关重要。
Skeletal myogenesis in the embryo is regulated by the coordinated expression of the MyoD family of muscle regulatory factors (MRFs). MyoD and Myf-5, which are the primary muscle lineage-determining factors, function in a partially redundant manner to establish muscle progenitor cell identity. Previous diphtheria toxin (DTA)-mediated ablation studies showed that MyoD+ progenitors rescue myogenesis in embryos in which Myf-5-expressing cells were targeted for ablation, raising the possibility that the regulative behavior of distinct, MRF-expressing populations explains the functional compensatory activities of these MRFs. Using MyoDiCre mice, we show that DTA-mediated ablation of MyoD-expressing cells results in the cessation of myogenesis by embryonic day 12.5 (E12.5), as assayed by myosin heavy chain (MyHC) and Myogenin staining. Importantly, MyoDiCre/+;R26DTA/+ embryos exhibited a concomitant loss of Myf-5+ progenitors, indicating that the vast majority of Myf-5+ progenitors express MyoD, a conclusion consistent with immunofluorescence analysis of Myf-5 protein expression in MyoDiCre lineage-labeled embryos. Surprisingly, staining for the paired box transcription factor, Pax7, which functions genetically upstream of MyoD in the trunk and is a marker for fetal myoblasts and satellite cell progenitors, was also lost by E12.5. Specific ablation of differentiating skeletal muscle in ACTA1Cre;R26DTA/+ embryos resulted in comparatively minor effects on MyoD+, Myf-5+ and Pax7+ progenitors, indicating that cell non-autonomous effects are unlikely to explain the rapid loss of myogenic progenitors in MyoDiCre/+;R26DTA/+ embryos. We conclude that the vast majority of myogenic populations transit through a MyoD+ state, and that MyoD+ progenitors are essential for myogenesis and stem cell development.
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影响因子：
2.7
作者：
Biressi, Stefano;Bjornson, Christopher R. R.;Carlig, Poppy M. M.;Nishijo, Koichi;Keller, Charles;Rando, Thomas A.
通讯作者：
Rando, Thomas A.
影响因子：
10.5
作者：
Kassar-Duchossoy, L;Giacone, E;Tajbakhsh, S
通讯作者：
Tajbakhsh, S
影响因子：
4.6
作者：
Lepper, Christoph;Partridge, Terence A.;Fan, Chen-Ming
通讯作者：
Fan, Chen-Ming
影响因子：
4.6
作者：
Gensch, Nicole;Borchardt, Thilo;Braun, Thomas
通讯作者：
Braun, Thomas
影响因子：
56.9
作者：
GOLDHAMER, DJ;FAERMAN, A;EMERSON, CP
通讯作者：
EMERSON, CP