So Shuhei, Asakawa Masayo, Sawa Hitoshi
Multicellular Organization Laboratory, Department of Gene Function and Phenomics, National Institute of Genetics, Research Organization of Information and Systems (ROIS), Mishima, Japan.
Department of Genetics, School of Life Science, SOKENDAI (The Graduate University for Advanced Studies), Mishima, Japan.
Elife. 2024 Nov 1;13:e103035. doi: 10.7554/eLife.103035.
Organogenesis requires the proper production of diverse cell types and their positioning/migration. However, the coordination of these processes during development remains poorly understood. The gonad in exhibits a mirror-symmetric structure guided by the migration of distal tip cells (DTCs), which result from asymmetric divisions of somatic gonadal precursors (SGPs; Z1 and Z4). We found that the polarity of Z1 and Z4, which possess mirror-symmetric orientation, is controlled by the redundant functions of the LIN-17/Frizzled receptor and three Wnt proteins (CWN-1, CWN-2, and EGL-20) with distinct functions. In mutants, CWN-2 promotes normal polarity in both Z1 and Z4, while CWN-1 promotes reverse and normal polarity in Z1 and Z4, respectively. In contrast, EGL-20 inhibits the polarization of both Z1 and Z4. In triple mutants with a polarity reversal of Z1, DTCs from Z1 frequently miss-migrate to the posterior side. Our further analysis demonstrates that the mis-positioning of DTCs in the gonad due to the polarity reversal of Z1 leads to mis-migration. Similar mis-migration was also observed in ) animals producing ectopic DTCs. These results highlight the role of Wnt signaling in coordinating the production and migration of DTCs to establish a mirror-symmetric organ.
器官发生需要正确产生多种细胞类型并使其定位/迁移。然而,在发育过程中这些过程的协调仍知之甚少。线虫中的性腺呈现出一种镜像对称结构,由远端末梢细胞(DTCs)的迁移引导,而DTCs源自体细胞性腺前体(SGPs;Z1和Z4)的不对称分裂。我们发现,具有镜像对称取向的Z1和Z4的极性由LIN-17/卷曲受体和三种具有不同功能的Wnt蛋白(CWN-1、CWN-2和EGL-20)的冗余功能控制。在突变体中,CWN-2促进Z1和Z4的正常极性,而CWN-1分别促进Z1的反向极性和Z4的正常极性。相反,EGL-20抑制Z1和Z4的极化。在Z1极性反转的三重突变体中,来自Z1的DTCs经常错误迁移到后侧。我们的进一步分析表明,由于Z1的极性反转导致性腺中DTCs的定位错误会导致错误迁移。在产生异位DTCs的动物中也观察到了类似的错误迁移。这些结果突出了Wnt信号在协调DTCs的产生和迁移以建立镜像对称器官中的作用。