Sai XiaoRei, Ladher Raj K
Laboratory for Sensory Development, RIKEN Kobe Institute, Center for Developmental Biology, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe, 640-0047, Japan.
Curr Biol. 2008 Jul 8;18(13):976-81. doi: 10.1016/j.cub.2008.05.049. Epub 2008 Jun 26.
Changes in the cytoskeletal architecture underpin the dynamic changes in tissue shape that occur during development. It is clear that such changes must be coordinated so that individual cell behaviors are synchronized; however, the mechanisms by which morphogenesis is instructed and coordinated are unknown. After its induction in non-neural ectoderm, the inner ear undergoes morphogenesis, being transformed from a flat ectodermal disk on the surface of the embryo to a hollowed sphere embedded in the head. We provide evidence that this shape change relies on extrinsic signals subsequent to genetic specification. By using specific inhibitors, we find that local fibroblast growth factor (FGF) signaling triggers a phosphorylation cascade that activates basal myosin II through the activation of phospholipase Cgamma. Myosin II exhibits a noncanonical activity that results in the local depletion of actin filaments. Significantly, the resulting apical actin enrichment drives morphogenesis of the inner ear. Thus, FGF signaling directly exerts profound cytoskeletal effects on otic cells, coordinating the morphogenesis of the inner ear. The iteration of this morphogenetic signaling system suggests that it is a more generally applicable mechanism in other epithelial tissues undergoing shape change.
细胞骨架结构的变化是发育过程中组织形态动态变化的基础。显然，这种变化必须得到协调，以使单个细胞的行为同步；然而，形态发生的指导和协调机制尚不清楚。在内耳于非神经外胚层中诱导形成后，它经历形态发生，从胚胎表面的扁平外胚层盘转变为嵌入头部的中空球体。我们提供的证据表明，这种形状变化依赖于基因特化后的外在信号。通过使用特异性抑制剂，我们发现局部成纤维细胞生长因子（FGF）信号触发了一个磷酸化级联反应，该反应通过激活磷脂酶Cγ来激活基底肌球蛋白II。肌球蛋白II表现出一种非典型活性，导致肌动蛋白丝的局部消耗。重要的是，由此产生的顶端肌动蛋白富集驱动了内耳的形态发生。因此，FGF信号直接对内耳细胞产生深远的细胞骨架效应，协调内耳的形态发生。这种形态发生信号系统的迭代表明，它是其他正在经历形状变化的上皮组织中一种更普遍适用的机制。
