Gastrulation is a dynamic tissue-remodeling process occurring during early development and fundamental to the later organogenesis. It involves both chemical signals and physical factors. Although much is known about the molecular pathways involved, the roles of physical forces in regulating cellular behavior and tissue remodeling during gastrulation have just begun to be explored. Here, we characterized the force generated by the leading edge mesoderm (LEM) that migrates preceding axial mesoderm (AM), and investigated the contribution of LEM during Xenopus gastrulation. First, we constructed an assay system using micro-needle which could measure physical forces generated by the anterior migration of LEM, and estimated the absolute magnitude of the force to be 20-80nN. Second, laser ablation experiments showed that LEM could affect the force distribution in the AM (i.e. LEM adds stretch force on axial mesoderm along anterior-posterior axis). Third, migrating LEM was found to be necessary for the proper gastrulation cell movements and the establishment of organized notochord structure; a reduction of LEM migratory activity resulted in the disruption of mediolateral cell orientation and convergence in AM. Finally, we found that LEM migration cooperates with Wnt/PCP to form proper notochord. These results suggest that the force generated by the directional migration of LEM is transmitted to AM and assists the tissue organization of notochord in vivo independently of the regulation by Wnt/PCP. We propose that the LEM may have a mechanical role in aiding the AM elongation through the rearrangement of force distribution in the dorsal marginal zone.

译文

胃形成是一个动态的组织重塑过程,发生在早期发育过程中,是后期器官发生的基础。它涉及化学信号和物理因素。尽管人们对所涉及的分子途径了解很多,但在胃形成过程中,物理力在调节细胞行为和组织重塑中的作用才刚刚开始探索。在这里,我们表征了在轴向中胚层 (AM) 之前迁移的前缘中胚层 (LEM) 产生的力,并研究了LEM在非洲爪蟾胃形成过程中的贡献。首先,我们使用微针构建了一个测定系统,该系统可以测量由LEM的前迁移产生的物理力,并估计该力的绝对大小为20-80nn。其次,激光消融实验表明,LEM可以影响AM中的力分布 (即LEM沿前后轴在轴向中胚层上增加拉伸力)。第三,发现迁移LEM对于适当的胃形成细胞运动和建立有组织的脊索结构是必要的; LEM迁移活动的减少导致AM中上外侧细胞取向和会聚的破坏。最后,我们发现LEM迁移与Wnt/PCP合作形成适当的脊索。这些结果表明,由LEM的定向迁移产生的力传递到AM,并独立于Wnt/PCP的调节而有助于体内脊索的组织组织。我们建议,LEM可能具有机械作用,可通过重新排列背侧边缘区的力分布来帮助AM伸长。

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