CABD (CSIC-Universidad Pablo de Olavide-JA), Sevilla 41013, Spain; Randall Centre for Cell and Molecular Biophysics, King's College London, London SE5 9AP, UK.
Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK.
Cell Rep. 2017 Nov 7;21(6):1461-1470. doi: 10.1016/j.celrep.2017.10.047.
The most prominent developmental function attributed to the extracellular matrix (ECM) is cell migration. While cells in culture can produce ECM to migrate, the role of ECM in regulating developmental cell migration is classically viewed as an exogenous matrix presented to the moving cells. In contrast to this view, we show here that Drosophila embryonic hemocytes deposit their own laminins in streak-like structures to migrate efficiently throughout the embryo. With the help of transplantation experiments, live microscopy, and image quantification, we demonstrate that autocrine-produced laminin regulates hemocyte migration by controlling lamellipodia dynamics, stability, and persistence. Proper laminin deposition is regulated by the RabGTPase Rab8, which is highly expressed and required in hemocytes for lamellipodia dynamics and migration. Our results thus support a model in which, during embryogenesis, the Rab8-regulated autocrine deposition of laminin reinforces directional and effective migration by stabilizing cellular protrusions and strengthening otherwise transient adhesion states.
细胞外基质（ECM）最重要的发育功能是细胞迁移。虽然培养中的细胞可以产生 ECM 来迁移，但 ECM 调节发育中细胞迁移的作用通常被视为向移动细胞提供的外源性基质。与这种观点相反，我们在这里表明，果蝇胚胎血细胞在条纹状结构中沉积它们自己的层粘连蛋白，以有效地在整个胚胎中迁移。借助于移植实验、活体显微镜和图像定量，我们证明自分泌产生的层粘连蛋白通过控制片状伪足的动力学、稳定性和持久性来调节血细胞的迁移。适当的层粘连蛋白沉积受 RabGTPase Rab8 的调节，Rab8 在血细胞中高表达，对于片状伪足的动力学和迁移是必需的。因此，我们的结果支持这样一种模型，即在胚胎发生过程中，Rab8 调节的层粘连蛋白的自分泌沉积通过稳定细胞突起和增强原本短暂的粘附状态来增强定向和有效的迁移。
