Lecaudey Virginie, Cakan-Akdogan Gulcin, Norton William H J, Gilmour Darren
European Molecular Biology Laboratory, Meyerhofstrasse 1, Heidelberg, Germany.
Development. 2008 Aug;135(16):2695-705. doi: 10.1242/dev.025981. Epub 2008 Jul 3.
The collective migration of cells in the form of cohesive tissues is a hallmark of both morphogenesis and repair. The extrinsic cues that direct these complex migrations usually act by regulating the dynamics of a specific subset of cells, those at the leading edge. Given that normally the function of tissue migration is to lay down multicellular structures, such as branched epithelial networks or sensory organs, it is surprising how little is known about the mechanisms that organize cells behind the leading edge. Cells of the zebrafish lateral line primordium switch from mesenchyme-like leader cells to epithelial rosettes that develop into mechanosensory organs. Here, we show that this transition is regulated by an Fgf signaling circuit that is active within the migrating primordium. Point sources of Fgf ligand drive surrounding cells towards a ;non-leader' fate by increasing their epithelial character, a prerequisite for rosette formation. We demonstrate that the dynamic expression of Fgf ligands determines the spatiotemporal pattern of epithelialization underlying sensory organ formation in the lateral line. Furthermore, this work uncovers a surprising link between internal tissue organization and collective migration.
细胞以黏附组织的形式进行集体迁移是形态发生和修复的一个标志。引导这些复杂迁移的外在信号通常通过调节特定细胞亚群（即前沿细胞）的动态来发挥作用。鉴于组织迁移的正常功能是形成多细胞结构，如分支上皮网络或感觉器官，令人惊讶的是，对于组织前沿后方细胞的组织机制我们知之甚少。斑马鱼侧线原基的细胞从间充质样的前沿细胞转变为上皮玫瑰花结，进而发育成机械感觉器官。在这里，我们表明这种转变受一个在迁移原基内活跃的Fgf信号通路调控。Fgf配体的点源通过增加周围细胞的上皮特征，驱使它们走向“非前沿”命运，而上皮特征是玫瑰花结形成的一个先决条件。我们证明Fgf配体的动态表达决定了侧线感觉器官形成过程中上皮化的时空模式。此外，这项研究揭示了内部组织组织与集体迁移之间令人惊讶的联系。
