6月19日,PNAS杂志在线发表了中国科学院生物物理研究所欧光朔课题组关于线虫神经细胞定向迁移的研究成果。
线虫右侧的神经前体细胞QR及其后代细胞(QR.x)向线虫的头部迁移,而左侧的神经前体细胞QL及其后代细胞(QL.x)向线虫尾部迁移(图A)。Wnt信号通路和Hox基因mab-5调控QL.x 向线虫尾部的迁移,而关于调控QR.x向线虫头部迁移的研究相对缺乏。欧光朔课题组利用线虫正向遗传筛选,发现一个保守的单次跨膜蛋白MIG-13以细胞自主性的方式特异的调控QR.x向线虫头部的迁移。时序荧光显微成像揭示了mig-13调控迁移细胞中微丝骨架的极性排布;Hox基因lin-39促进mig-13 在向前迁移的QR.x中表达,而Wnt信号通路和mab-5抑制mig-13在QL.x中的表达(图B)。这项工作为研究线虫神经细胞迁移指出了方向,也可为哺乳类MIG-13同源蛋白的研究提供借鉴。
王香明博士为该文第一作者。该研究得到科技部国家重点基础研究973计划、国家自然科学基金、北京市自然科学基金及中组部“青年千人计划” 资助。
A.线虫Q神经前体细胞迁移模式图。Hox基因lin-39控制线虫身体前部发育,而另一个Hox基因mab-5控制线虫身体后部发育。B. Wnt信号、Hox基因和MIG-13调控Q细胞迁移的模式图。(生物谷Bioon.com)
Nature Genetics, doi:10.1073/pnas.1301849110
Transmembrane protein MIG-13 links the Wntsignaling and Hox genes to the cell polarity in neuronal migration
Xiangming Wang, Fanli Zhou, Sijing Lv, Peishan Yi, Zhiwen Zhu, Yihong Yang, Guoxin Feng, Wei Li, and Guangshuo
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, cellautonomously 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.xanterior 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.