Llense Flora, Martín-Blanco Enrique
Instituto de Biología Molecular de Barcelona, Consejo Superior de Investigaciones Científicas, Parc Cientific de Barcelona, Baldiri Reixac 10, Barcelona 08028, Spain.
Curr Biol. 2008 Apr 8;18(7):538-44. doi: 10.1016/j.cub.2008.03.029.
Collective cell movement is a mechanism for invasion identified in many developmental events. Examples include the movement of lateral-line neurons in Zebrafish, cells in the inner blastocyst, and metastasis of epithelial tumors [1]. One key model to study collective migration is the movement of border cell clusters in Drosophila. Drosophila egg chambers contain 15 nurse cells and a single oocyte surrounded by somatic follicle cells. At their anterior end, polar cells recruit several neighboring follicle cells to form the border cell cluster [2]. By stage 9, and over 6 hr, border cells migrate as a cohort between nurse cells toward the oocyte. The specification and directionality of border cell movement are regulated by hormonal and signaling mechanisms [3]. However, how border cells are held together while they migrate is not known. Here, we show that a negative-feedback loop controlling JNK activity regulates border cell cluster integrity. JNK signaling modulates contacts between border cells and between border cells and substratum to sustain collective migration by regulating several effectors including the polarity factor Bazooka and the cytoskeletal adaptor D-Paxillin. We anticipate a role for the JNK pathway in controlling collective cell movements in other morphogenetic and clinical models.
集体细胞运动是在许多发育事件中发现的一种侵袭机制。例子包括斑马鱼侧线神经元的运动、内胚层囊胚中的细胞以及上皮肿瘤的转移[1]。研究集体迁移的一个关键模型是果蝇中边界细胞簇的运动。果蝇卵室包含15个滋养细胞和一个被体细胞滤泡细胞包围的卵母细胞。在其前端,极性细胞招募几个相邻的滤泡细胞形成边界细胞簇[2]。到第9阶段,在6个多小时的时间里,边界细胞作为一个群体在滋养细胞之间朝着卵母细胞迁移。边界细胞运动的特化和方向性由激素和信号机制调节[3]。然而,边界细胞在迁移时如何聚集在一起尚不清楚。在这里,我们表明控制JNK活性的负反馈回路调节边界细胞簇的完整性。JNK信号传导通过调节包括极性因子巴祖卡和细胞骨架衔接蛋白D-帕克斯林在内的几种效应器,调节边界细胞之间以及边界细胞与基质之间的接触,以维持集体迁移。我们预计JNK途径在控制其他形态发生和临床模型中的集体细胞运动中发挥作用。