JNK signaling controls border cell cluster integrity and collective cell migration

JNK signaling controls border cell cluster integrity and collective cell migration
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DOI:
10.1016/j.cub.2008.03.029
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发表时间:
2008-04-08
期刊:
影响因子:
9.2
通讯作者:
Martin-Blanco, Enrique
Martin-Blanco, Enrique
中科院分区:
生物学1区
文献类型:
--
作者:
Llense, Flora;Martin-Blanco, Enrique

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集体细胞运动是在许多发育事件中发现的一种侵袭机制。例如斑马鱼侧线神经元的运动、囊胚内细胞的运动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缘细胞簇的运动。果蝇的卵室包含15个滋养细胞和一个被体细胞卵泡细胞包围的卵母细胞。在其前端,极细胞招募几个邻近的卵泡细胞形成边缘细胞簇[2]。到第9阶段,经过6个多小时,边缘细胞作为一个群体在滋养细胞之间向卵母细胞迁移。边缘细胞运动的特化和方向性受激素和信号机制的调控[3]。然而,边缘细胞在迁移时是如何聚集在一起的尚不清楚。在此,我们表明一个控制JNK活性的负反馈回路调节边缘细胞簇的完整性。JNK信号通过调节包括极性因子Bazooka和细胞骨架衔接蛋白D - Paxillin在内的几种效应因子,调节边缘细胞之间以及边缘细胞与基质之间的接触,以维持集体迁移。我们预期JNK通路在其他形态发生和临床模型中对控制集体细胞运动起作用。
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.