6月19日,PNAS雜志在線發(fā)表了中國科學(xué)院生物物理研究所歐光朔課題組關(guān)于線蟲神經(jīng)細(xì)胞定向遷移的研究成果,。
線蟲右側(cè)的神經(jīng)前體細(xì)胞QR及其后代細(xì)胞(QR.x)向線蟲的頭部遷移,而左側(cè)的神經(jīng)前體細(xì)胞QL及其后代細(xì)胞(QL.x)向線蟲尾部遷移(圖A),。Wnt信號通路和Hox基因mab-5調(diào)控QL.x 向線蟲尾部的遷移,,而關(guān)于調(diào)控QR.x向線蟲頭部遷移的研究相對缺乏。歐光朔課題組利用線蟲正向遺傳篩選,,發(fā)現(xiàn)一個保守的單次跨膜蛋白MIG-13以細(xì)胞自主性的方式特異的調(diào)控QR.x向線蟲頭部的遷移,。時序熒光顯微成像揭示了mig-13調(diào)控遷移細(xì)胞中微絲骨架的極性排布;Hox基因lin-39促進(jìn)mig-13 在向前遷移的QR.x中表達(dá),,而Wnt信號通路和mab-5抑制mig-13在QL.x中的表達(dá)(圖B),。這項工作為研究線蟲神經(jīng)細(xì)胞遷移指出了方向,也可為哺乳類MIG-13同源蛋白的研究提供借鑒,。
王香明博士為該文第一作者,。該研究得到科技部國家重點基礎(chǔ)研究973計劃、國家自然科學(xué)基金,、北京市自然科學(xué)基金及中組部“青年千人計劃” 資助,。
A.線蟲Q神經(jīng)前體細(xì)胞遷移模式圖。Hox基因lin-39控制線蟲身體前部發(fā)育,,而另一個Hox基因mab-5控制線蟲身體后部發(fā)育,。B. Wnt信號、Hox基因和MIG-13調(diào)控Q細(xì)胞遷移的模式圖,。(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.