Transmembrane protein MIG-13 links the Wnt signaling and Hox genes to the cell polarity in neuronal migration
Transmembrane protein MIG-13 links the Wnt signaling and Hox genes to the cell polarity in neuronal migration
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DOI：
10.1073/pnas.1301849110
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发表时间：
2013-06
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影响因子：
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通讯作者：
Xiangming Wang;Fanli Zhou;Si-Xu Lv;Peishan Yi;Zhiwen Zhu;Yihong Yang;Guoxin Feng;Wei Li-;Guangshuo Ou
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文献类型：
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作者：
Xiangming Wang;Fanli Zhou;Si-Xu Lv;Peishan Yi;Zhiwen Zhu;Yihong Yang;Guoxin Feng;Wei Li-;Guangshuo Ou
细胞定向迁移是神经发育的一个基本过程。在秀丽隐杆线虫中，动物左侧（QL）和右侧（QR）的Q神经母细胞产生沿沿着前后体轴向相反方向迁移的细胞。同源框（Hox）基因lin-39促进QR后代（QR.x）的前向迁移，而经典Wnt信号通路激活另一个Hox基因mAb-5，以确保QL后代（QL.x）的后向迁移。然而，LIN-39和MAB-5的调控靶点仍然难以捉摸。在这里，我们发现，ESTA-13，进化上保守的跨膜蛋白，细胞自主调节的肌动蛋白细胞骨架的不对称分布在领先的迁移边缘。我们将mig-13鉴定为LIN-39和MAB-5的细胞靶标。LIN-39通过与mig-13启动子结合并促进mig-13表达来建立QR.x前极性，而MAB-5通过与lin-39启动子结合并下调lin-39和mig-13表达来抑制QL.x前极性。因此，β-13将引导迁移的Wnt信号传导和Hox基因连接到肌动蛋白细胞骨架，肌动蛋白细胞骨架在神经元迁移中执行运动性反应。
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.