Mesogenin 1 is a master regulator of paraxial presomitic mesoderm differentiation
Mesogenin 1 is a master regulator of paraxial presomitic mesoderm differentiation
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DOI：
10.1242/dev.110908
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发表时间：
2014-11-01
期刊：
影响因子：
4.6
通讯作者：
Yamaguchi, Terry P.
中科院分区：
文献类型：
--
作者：
Chalamalasetty, Ravindra B.;Garriock, Robert J.;Yamaguchi, Terry P.
神经中胚层(NM)干细胞产生神经和旁胚体前中胚层(PSM)细胞，它们分别是脊髓和躯干和尾部肌肉骨骼的祖细胞。Wnt调控的碱性螺旋-环-螺旋(BHLH)转录因子Mesgenin 1(Msgn1)与T-box基因协同调控斑马鱼PSM的形成，但机制尚不清楚。我们在这里表明，在小鼠中，Msgn1单独通过直接激活转录程序来控制PSM的分化，这些转录程序定义了PSM的身份、上皮-间充质转化、运动和分割。Msgn1在NM干细胞体内的强制表达减少了其后代对神经管的贡献，并显著扩大了未分段的间充质PSM，同时阻碍了体细胞发育和脊索分化。Msgn1的表达足以部分挽救Wnt3a(-/-)胚胎的PSM分化，表明Msgn1在Wnt3a下游是PSM分化的主要调节因子。我们的数据为细胞命运决定是如何由单一转录调控因子的表达强加的提供了新的见解。
Neuromesodermal (NM) stem cells generate neural and paraxial presomitic mesoderm (PSM) cells, which are the respective progenitors of the spinal cord and musculoskeleton of the trunk and tail. The Wnt-regulated basic helix-loop-helix (bHLH) transcription factor mesogenin 1 (Msgn1) has been implicated as a cooperative regulator working in concert with T-box genes to control PSM formation in zebrafish, although the mechanism is unknown. We show here that, in mice, Msgn1 alone controls PSM differentiation by directly activating the transcriptional programs that define PSM identity, epithelial-mesenchymal transition, motility and segmentation. Forced expression of Msgn1 in NM stem cells in vivo reduced the contribution of their progeny to the neural tube, and dramatically expanded the unsegmented mesenchymal PSM while blocking somitogenesis and notochord differentiation. Expression of Msgn1 was sufficient to partially rescue PSM differentiation in Wnt3a(-/-) embryos, demonstrating that Msgn1 functions downstream of Wnt3a as the master regulator of PSM differentiation. Our data provide new insights into how cell fate decisions are imposed by the expression of a single transcriptional regulator.