Fat2 and Lar Define a Basally Localized Planar Signaling System Controlling Collective Cell Migration.
Fat2 and Lar Define a Basally Localized Planar Signaling System Controlling Collective Cell Migration.
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DOI：
10.1016/j.devcel.2017.02.003
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发表时间：
2017-03-13
影响因子：
11.8
通讯作者：
Horne-Badovinac S
中科院分区：
文献类型：
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作者：
Barlan K;Cetera M;Horne-Badovinac S
上皮细胞的集体迁移是多种组织重塑事件的基础，但协调个体细胞集体迁移行为的机制在很大程度上是未知的。研究果蝇滤泡上皮，我们发现钙粘蛋白Fat2和受体酪氨酸磷酸酶Lar在平面信号系统中起作用，协调相邻细胞之间的前后缘动态。来自每个细胞后缘的Fat2信号诱导细胞后缘的前缘突起，部分原因是通过稳定这些细胞中的Lar定位。相反，每个细胞的前缘发出的信号刺激前方细胞的后缘收缩。在亚细胞蛋白定位方面，Fat2/Lar信号与平面细胞极性信号相似；然而，Fat2/Lar信号介导邻近细胞之间的短距离通信，而不是在组织中传递远程信息。这项工作定义了促进上皮迁移的关键机制，并建立了平面细胞-细胞信号传导的不同范式。Barlan和他的同事研究了钙粘蛋白Fat2和酪氨酸磷酸酶受体Lar在果蝇卵腔中如何促进上皮细胞的迁移。他们表明，这些蛋白质构成了平面信号系统的核心，该系统协调相邻细胞之间的前缘和后缘动态。
Collective migration of epithelial cells underlies diverse tissue remodeling events, but the mechanisms that coordinate individual cell migratory behaviors for collective movement are largely unknown. Studying the Drosophila follicular epithelium, we show that the cadherin Fat2 and the receptor tyrosine phosphatase Lar function in a planar signaling system that coordinates leading and trailing edge dynamics between neighboring cells. Fat2 signals from each cell’s trailing edge to induce leading edge protrusions in the cell behind, in part, by stabilizing Lar’s localization in these cells. Conversely, Lar signals from each cell’s leading edge to stimulate trailing edge retraction in the cell ahead. Fat2/Lar signaling is similar to planar cell polarity signaling in terms of subcellular protein localization; however, Fat2/Lar signaling mediates short-range communication between neighboring cells instead of transmitting long-range information across a tissue. This work defines a key mechanism promoting epithelial migration and establishes a different paradigm for planar cell-cell signaling. Barlan and colleagues examine how the cadherin Fat2 and the receptor tyrosine phosphatase Lar promote epithelial migration in the context of the Drosophila egg chamber. They show that these proteins form the core of a planar signaling system that coordinates leading and trailing edge dynamics between neighboring cells.