Regulation of dorsal somitic cell fates: BMPs and Noggin control the timing and pattern of myogenic regulator expression
Regulation of dorsal somitic cell fates: BMPs and Noggin control the timing and pattern of myogenic regulator expression
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DOI：
10.1101/gad.12.3.290
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发表时间：
1998-02-01
影响因子：
10.5
通讯作者：
Lassar, AB
中科院分区：
文献类型：
--
作者：
Reshef, R;Maroto, M;Lassar, AB
以前的工作表明，来自神经管，脊索和表面外胚层的信号促进体节肌的发生。在这里，我们表明，体节肌的肌肉发生是负调控以及BMP信号转导抑制激活的MyoD和Myf5在Pax3表达细胞。此外，我们表明，BMP拮抗剂头蛋白内表达的dermomyotome，其中Pax3表达细胞首先启动MyoD和Myf5的表达，从而产生肌节细胞在内侧体节的背内侧唇。与位于背侧神经管附近的背内侧皮肌瘤细胞中Noggin的表达一致，我们发现体节与编程分泌Wnt 1的成纤维细胞共培养，Wnt 1在背侧神经管中表达，可以诱导Semitic Noggin表达。体节外侧头蛋白的异位表达显著地将MtoD表达扩展到体节的外侧区域，抑制该组织中的Pax3表达，并诱导外侧肌节的形成。总之，我们的研究结果表明，体节内的肌肉发生的时间和位置是由BMP活性的相对水平和BMP拮抗剂的局部表达控制的。
Previous work has indicated that signals from the neural tube, notochord, and surface ectoderm promote somitic myogenesis. Here, we show that somitic myogenesis is under negative regulation as well; BMP signaling serves to inhibit the activation of MyoD and Myf5 in Pax3-expressing cells. Furthermore, we show that the BMP antagonist Noggin is expressed within the dorsomedial lip of the dermomyotome, where Pax3-expressing cells first initiate the expression of MyoD and Myf5 to give rise to myotomal cells in the medial somite. Consistent with the expression of Noggin in dorsomedial dermomyotomal cells that lie adjacent to the dorsal neural tube, we have found that coculture of somites with fibroblasts programmed to secrete Wnt1, which is expressed in dorsal neural tube, call induce semitic Noggin expression. Ectopic expression of Noggin lateral to the somite dramatically expands MtoD expression into the lateral regions of the somite, represses Pax3 expression in this tissue, and induces formation of a lateral myotome. Together, our findings indicate that the timing and location of myogenesis within the somite is controlled by relative levels of BMP activity and localized expression of a BMP antagonist.