Differential activation of Myf5 and MyoD by different Wnts in explants of mouse paraxial mesoderm and the later activation of myogenesis in the absence of Myf5.
Differential activation of Myf5 and MyoD by different Wnts in explants of mouse paraxial mesoderm and the later activation of myogenesis in the absence of Myf5.
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发表时间：
1998-11
期刊：
影响因子：
4.6
通讯作者：
S. Tajbakhsh;U. Borello;E. Vivarelli;R. Kelly;J. Papkoff;D. Duprez;M. Buckingham;G. Cossu
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文献类型：
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作者：
S. Tajbakhsh;U. Borello;E. Vivarelli;R. Kelly;J. Papkoff;D. Duprez;M. Buckingham;G. Cossu
在新形成的体节中，肌发生的激活依赖于来自邻近组织的信号，即轴向结构（神经管和脊索）和背外胚层。在小鼠胚胎的近轴中胚层外植体中，轴向结构优先通过Myf5依赖性途径激活肌发生，背侧外胚层优先通过MyoD依赖性途径激活肌发生。在这里，我们报告说，表达Wnt1的细胞将优先激活Myf5，而表达Wnt7a的细胞将优先激活MyoD。在早期胚胎中，Wnt 1在背侧神经管中表达，Wnt 7a在背侧外胚层中表达，因此两者都可能在体内分别激活Myf 5和MyoD。Wnt4、Wnt5a和Wnt6在近轴中胚层中发挥中间效应，等同地激活Myf 5和MyoD。Sonic Hedgehog在来自E8.5近轴中胚层的外植体中与Wnt1和Wnt7a两者协同作用，但在来自E9.5胚胎的外植体中不协同作用。通过不同的生肌途径的信号传导可以解释Myf5无效胚胎中肌肉形成的拯救，其不形成早期肌节，但后来发展轴上和轴下肌肉组织。未分割的近轴中胚层的外植体含有能够响应于从E10.5胚胎分离的神经管的信号传导而表达MyoD的生肌前体，E10.5胚胎是MyoD存在于整个胚胎中的发育阶段。生肌细胞不能响应来自不太成熟的神经管的信号而激活MyoD。总之，这些数据表明，不同的Wnt分子可以通过不同的途径激活肌生成，从而在空间和时间上精确调节肌生成前体的定型，以实现骨骼肌发育的正确模式。
Activation of myogenesis in newly formed somites is dependent upon signals derived from neighboring tissues, namely axial structures (neural tube and notochord) and dorsal ectoderm. In explants of paraxial mesoderm from mouse embryos, axial structures preferentially activate myogenesis through a Myf5-dependent pathway and dorsal ectoderm preferentially through a MyoD-dependent pathway. Here we report that cells expressing Wnt1 will preferentially activate Myf5 while cells expressing Wnt7a will preferentially activate MyoD. Wnt1 is expressed in the dorsal neural tube and Wnt7a in dorsal ectoderm in the early embryo, therefore both can potentially act in vivo to activate Myf5 and MyoD, respectively. Wnt4, Wnt5a and Wnt6 exert an intermediate effect activating both Myf5 and MyoD equivalently in paraxial mesoderm. Sonic Hedgehog synergises with both Wnt1 and Wnt7a in explants from E8.5 paraxial mesoderm but not in explants from E9.5 embryos. Signaling through different myogenic pathways may explain the rescue of muscle formation in Myf5 null embryos, which do not form an early myotome but later develop both epaxial and hypaxial musculature. Explants of unsegmented paraxial mesoderm contain myogenic precursors capable of expressing MyoD in response to signaling from a neural tube isolated from E10.5 embryos, the developmental stage when MyoD is present throughout the embryo. Myogenic cells cannot activate MyoD in response to signaling from a less mature neural tube. Together these data suggest that different Wnt molecules can activate myogenesis through different pathways such that commitment of myogenic precursors is precisely regulated in space and time to achieve the correct pattern of skeletal muscle development.