Université Côte d'Azur, CNRS, Inserm, Institut de Biologie Valrose, Nice 06108, France
Université Côte d'Azur, CNRS, Inserm, Institut de Biologie Valrose, Nice 06108, France.
Development. 2018 Jul 30;145(14):dev161117. doi: 10.1242/dev.161117.
Understanding how different cell types acquire their motile behaviour is central to many normal and pathological processes. border cells represent a powerful model for addressing this issue and to specifically decipher the mechanisms controlling collective cell migration. Here, we identify the Insulin/Insulin-like growth factor signalling (IIS) pathway as a key regulator in controlling actin dynamics in border cells, independently of its function in growth control. Loss of IIS activity blocks the formation of actin-rich long cellular extensions that are important for the delamination and the migration of the invasive cluster. We show that IIS specifically activates the expression of the actin regulator , the homolog of Profilin, which is essential for promoting the formation of actin extensions and migration through the egg chamber. In this process, the transcription factor FoxO acts as a repressor of expression. Altogether, these results show that local activation of IIS controls collective cell migration through regulation of actin homeostasis and protrusion dynamics.
了解不同类型的细胞如何获得其运动行为对于许多正常和病理过程至关重要。 边缘细胞是解决这一问题的有力模型,可专门解析控制细胞集体迁移的机制。在这里,我们确定胰岛素/胰岛素样生长因子信号(IIS)途径是控制边缘细胞肌动蛋白动力学的关键调节剂,而与生长控制的功能无关。IIS 活性的丧失会阻止富含肌动蛋白的长细胞延伸的形成,而这些延伸对于侵袭群的分层和迁移很重要。我们表明,IIS 特异性地激活肌动蛋白调节剂的表达,即 Profilin 的同源物,这对于促进肌动蛋白延伸的形成和通过卵室的迁移是必不可少的。在这个过程中,转录因子 FoxO 作为 表达的抑制剂。总之,这些结果表明,IIS 的局部激活通过调节肌动蛋白动态平衡和突起动力学来控制细胞的集体迁移。