Keren Aviad, Bengal Eyal, Frank Dale
Department of Biochemistry, Rappaport Institute for Research in the Medical Sciences, Faculty of Medicine, Technion-Israel Institute of Technology, P.O. Box 9649, Haifa 31096, Israel.
Dev Biol. 2005 Dec 1;288(1):73-86. doi: 10.1016/j.ydbio.2005.09.020. Epub 2005 Oct 24.
The p38 MAPK signaling pathway is essential for skeletal muscle differentiation in tissue culture models. We demonstrate a novel role for p38 MAPK in myogenesis during early Xenopus laevis development. Interfering with p38 MAPK causes distinct defects in myogenesis. The initial expression of Myf5 is selectively blocked, while expression of MyoD is unaffected. Expression of a subset of muscle structural genes is reduced. Convergent extension movements are prevented and segmentation of the paraxial mesoderm is delayed, probably due to the failure of cells to withdraw from the cell cycle. Myotubes are properly formed; however, at later stages, they begin to degenerate, and the boundaries between somites disappear. Significant apoptotic cell death occurs in most parts of the somites. The ventral body wall muscle derived from migratory progenitor cells of the ventral somite region is poorly formed. Our data indicate that the developmental defects caused by p38alpha-knockdown were mediated by the loss of XMyf5 expression. Thus, this study identifies a specific intracellular pathway in which p38 MAPK and Myf5 proteins regulate a distinct myogenic program.
在组织培养模型中，p38丝裂原活化蛋白激酶（MAPK）信号通路对骨骼肌分化至关重要。我们证明了p38 MAPK在非洲爪蟾早期发育过程中的成肌作用中具有新的作用。干扰p38 MAPK会导致成肌过程出现明显缺陷。Myf5的初始表达被选择性阻断，而MyoD的表达不受影响。一部分肌肉结构基因的表达减少。汇聚延伸运动被阻止，轴旁中胚层的分割延迟，这可能是由于细胞未能退出细胞周期所致。肌管形成正常；然而，在后期，它们开始退化，体节之间的边界消失。在体节的大部分区域发生了显著的凋亡细胞死亡。源自腹侧体节区域迁移祖细胞的腹侧体壁肌肉形成不良。我们的数据表明，p38α基因敲低导致的发育缺陷是由XMyf5表达缺失介导的。因此，本研究确定了一条特定的细胞内途径，其中p38 MAPK和Myf5蛋白调节一个独特的成肌程序。
