Linker Claudia, Lesbros Cynthia, Stark Michael R, Marcelle Christophe
Laboratoire de Génétique et de Physiologie du Développement, Developmental Biology Institute of Marseille, CNRS UMR 6545, University Aix-Marseille II, Campus de Luminy, case 907, 13288 Marseille Cedex 09, France.
Development. 2003 Oct;130(20):4797-807. doi: 10.1242/dev.00688. Epub 2003 Aug 13.
In vertebrates, despite the evidence that extrinsic factors induce myogenesis in naive mesoderm, other experiments argue that the initiation of the myogenic program may take place independent of these factors. To resolve this discrepancy, we have re-addressed this issue, using short-term in vivo microsurgery and culture experiments in chick. Our results show that the initial expression of the muscle-specific markers Myf5 and MyoD is regulated in a mesoderm-autonomous fashion. The reception of a Wnt signal is required for MyoD, but not Myf5 expression; however, we show that the source of the Wnt signal is intrinsic to the mesoderm. Gain- and loss-of-function experiments indicate that Wnt5b, which is expressed in the presomitic mesoderm, represents the MyoD-activating cue. Despite Wnt5b expression in the presomitic mesoderm, MyoD is not expressed in this tissue: our experiments demonstrate that this is due to a Bmp inhibitory signal that prevents the premature expression of MyoD before somites form. Our results indicate that myogenesis is a multistep process which is initiated prior to somite formation in a mesoderm-autonomous fashion; as somites form, influences from adjacent tissues are likely to be required for maintenance and patterning of early muscles.
在脊椎动物中，尽管有证据表明外在因素可诱导原始中胚层发生肌生成，但其他实验表明，肌生成程序的启动可能独立于这些因素而发生。为了解决这一差异，我们利用鸡的短期体内显微手术和培养实验重新探讨了这个问题。我们的结果表明，肌肉特异性标志物Myf5和MyoD的初始表达是以中胚层自主方式调节的。MyoD的表达需要Wnt信号的接收，但Myf5的表达则不需要；然而，我们表明Wnt信号的来源是中胚层固有的。功能获得和功能丧失实验表明，在体节形成前的中胚层中表达的Wnt5b代表激活MyoD的信号。尽管Wnt5b在体节形成前的中胚层中表达，但MyoD在该组织中并不表达：我们的实验表明，这是由于一种Bmp抑制信号，该信号可防止在体节形成之前MyoD过早表达。我们的结果表明，肌生成是一个多步骤过程，它以中胚层自主方式在体节形成之前启动；随着体节的形成，早期肌肉的维持和模式形成可能需要来自相邻组织的影响。
