Department of Cell and Developmental Biology, Oregon Health & Science University, Portland, OR 97239, USA.
Development. 2012 Sep;139(17):3130-5. doi: 10.1242/dev.082271. Epub 2012 Jul 25.
Many morphogenetic movements during development require the formation of transient intermediates called rosettes. Within rosettes, cells are polarized with apical ends constricted towards the rosette center and nuclei basally displaced. Whereas the polarity and cytoskeletal machinery establishing these structures has been extensively studied, the extracellular cues and intracellular signaling cascades that promote their formation are not well understood. We examined how extracellular Fibroblast growth factor (Fgf) signals regulate rosette formation in the zebrafish posterior lateral line primordium (pLLp), a group of ∼100 cells that migrates along the trunk during embryonic development to form the lateral line mechanosensory system. During migration, the pLLp deposits rosettes from the trailing edge, while cells are polarized and incorporated into nascent rosettes in the leading region. Fgf signaling was previously shown to be crucial for rosette formation in the pLLp. We demonstrate that activation of Fgf receptor (Fgfr) induces intracellular Ras-MAPK, which is required for apical constriction and rosette formation in the pLLp. Inhibiting Fgfr-Ras-MAPK leads to loss of apically localized Rho-associated kinase (Rock) 2a, which results in failed actomyosin cytoskeleton activation. Using mosaic analyses, we show that a cell-autonomous Ras-MAPK signal is required for apical constriction and Rock2a localization. We propose a model whereby activated Fgfr signals through Ras-MAPK to induce apical localization of Rock2a in a cell-autonomous manner, activating the actomyosin network to promote apical constriction and rosette formation in the pLLp. This mechanism presents a novel cellular strategy for driving cell shape changes.
许多发育过程中的形态发生运动需要形成称为玫瑰花结的短暂中间体。在玫瑰花结中,细胞具有极性,顶端朝向玫瑰花结中心收缩,核基底位移。虽然已经广泛研究了建立这些结构的极性和细胞骨架机制,但促进它们形成的细胞外线索和细胞内信号级联仍未得到很好的理解。我们研究了细胞外成纤维细胞生长因子 (Fgf) 信号如何调节斑马鱼后外侧线原基 (pLLp) 中的玫瑰花结形成,pLLp 是一组约 100 个细胞,在胚胎发育过程中沿躯干迁移,形成侧线机械感觉系统。在迁移过程中,pLLp 从后缘沉积玫瑰花结,而细胞在前沿被极化并被纳入新形成的玫瑰花结中。先前的研究表明,Fgf 信号对于 pLLp 中的玫瑰花结形成至关重要。我们证明 Fgf 受体 (Fgfr) 的激活诱导细胞内 Ras-MAPK,这对于 pLLp 中的顶端收缩和玫瑰花结形成是必需的。抑制 Fgfr-Ras-MAPK 会导致 Rho 相关激酶 (Rock) 2a 的顶端定位丢失,从而导致肌动球蛋白细胞骨架激活失败。通过镶嵌分析,我们表明细胞自主的 Ras-MAPK 信号对于顶端收缩和 Rock2a 定位是必需的。我们提出了一个模型,即激活的 Fgfr 通过 Ras-MAPK 以细胞自主的方式诱导 Rock2a 的顶端定位,激活肌动球蛋白网络以促进 pLLp 中的顶端收缩和玫瑰花结形成。这种机制提出了一种新颖的细胞策略,用于驱动细胞形状变化。