Transmembrane protein MIG-13 links the Wnt signaling and Hox genes to the cell polarity in neuronal migration

作者：Xiangming Wang, Fanli Zhou, Sijing Lv, Peishan Yi, Zhiwen Zhu, Yihong Yang, Guoxin Feng, Wei Li, Guangshuo Ou · 发表于：Proceedings of the National Academy of Sciences · 年份：2013 · DOI：10.1073/pnas.1301849110 · 被引用次数：52 · 研究领域：Genetics, Aging, and Longevity in Model Organisms、Cellular Mechanics and Interactions、Pluripotent Stem Cells Research

Directional cell migration is a fundamental process in neural development. In Caenorhabditis elegans, Q neuroblasts on the left (QL) and right (QR) sides of the animal generate cells that migrate in opposite directions along the anteroposterior body axis. The homeobox (Hox) gene lin-39 promotes the anterior migration of QR descendants (QR.x), whereas the canonical Wnt signaling pathway activates another Hox gene, mab-5, to ensure the QL descendants' (QL.x) posterior migration. However, the regulatory targets of LIN-39 and MAB-5 remain elusive. Here, we showed that MIG-13, an evolutionarily conserved transmembrane protein, cell-autonomously regulates the asymmetric distribution of the actin cytoskeleton in the leading migratory edge. We identified mig-13 as a cellular target of LIN-39 and MAB-5. LIN-39 establishes QR.x anterior polarity by binding to the mig-13 promoter and promoting mig-13 expression, whereas MAB-5 inhibits QL.x anterior polarity by associating with the lin-39 promoter and downregulating lin-39 and mig-13 expression. Thus, MIG-13 links the Wnt signaling and Hox genes that guide migrations, to the actin cytoskeleton, which executes the motility response in neuronal migration.