Wagner J, Schmidt C, Nikowits W, Christ B
Institute of Anatomy, University of Freiburg, Freiburg, D-79001, Germany.
Dev Biol. 2000 Dec 1;228(1):86-94. doi: 10.1006/dbio.2000.9921.
Muscles of the body and bones of the axial skeleton derive from specialized regions of somites. Somite development is influenced by adjacent structures. In particular, the dorsal neural tube and the overlying ectoderm have been shown to be necessary for the induction of myogenic precursor cells in the dermomyotome. Members of the Wnt family of signaling molecules, which are expressed in the dorsal neural tube and the ectoderm, are postulated to be responsible for this process. It is shown here that ectopically implanted Wnt-1-, -3a-, and -4-expressing cells alter the process of somite compartmentalization in vivo. An enlarged dorsal compartment results from the implantation of Wnt-expressing cells ventrally between the neural tube/notochord and epithelial somites, at the expense of the ventral compartment, the sclerotome. Thus, ectopic Wnt expression is able to override the influence of ventralizing signals arising from notochord and floor plate. This shift of the border between the two compartments was identified by an increase in the domain of Pax-3 expression and a complete loss of Pax-1 expression in somites close to the ectopic Wnt signal. The expanded expression of MyoD and desmin provides evidence that it is the myotome which increases as a result of Wnt signaling. Paraxis expression is also drastically amplified after implantation of Wnt-expressing cells indicating that Wnts are involved in the formation and maintenance of somite epithelium and suggesting that Paraxis is activated through Wnt signaling pathways. Taken together these results suggest that ectopic Wnts disturb the normal balance of signaling molecules within the somite, resulting in an enhanced recruitment of somitic cells into the myogenic lineage.
身体的肌肉和中轴骨骼来源于体节的特定区域。体节的发育受到相邻结构的影响。特别是,背侧神经管和覆盖其上的外胚层已被证明是诱导皮肌节中肌源性前体细胞所必需的。在背侧神经管和外胚层中表达的Wnt信号分子家族成员被认为负责这一过程。本文表明,异位植入表达Wnt-1、-3a和-4的细胞会改变体内体节分隔的过程。在神经管/脊索和上皮性体节之间腹侧植入表达Wnt的细胞会导致背侧区室扩大,而腹侧区室(即生骨节)则相应减小。因此,异位Wnt表达能够克服来自脊索和底板的腹侧化信号的影响。通过靠近异位Wnt信号的体节中Pax-3表达域的增加和Pax-1表达的完全丧失,确定了两个区室之间边界的这种移动。MyoD和结蛋白表达的扩大表明,由于Wnt信号传导,增加的是肌节。在植入表达Wnt的细胞后,Paraxis的表达也大幅增强,这表明Wnts参与体节上皮的形成和维持,并提示Paraxis是通过Wnt信号通路被激活的。综合这些结果表明,异位Wnt扰乱了体节内信号分子的正常平衡,导致更多的体节细胞被招募到肌源性谱系中。