Fernandes Vilaiwan M, McCormack Kasandra, Lewellyn Lindsay, Verheyen Esther M
Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC V5A1S6, Canada.
Biological Sciences Department, Butler University, Indianapolis, IN 46208, USA.
Cell Rep. 2014 Dec 24;9(6):2043-55. doi: 10.1016/j.celrep.2014.11.041. Epub 2014 Dec 18.
During morphogenesis, extracellular signals trigger actomyosin contractility in subpopulations of cells to coordinate changes in cell shape. To illuminate the link between signaling-mediated tissue patterning and cytoskeletal remodeling, we study the progression of the morphogenetic furrow (MF), the wave of apical constriction that traverses the Drosophila eye imaginal disc preceding photoreceptor neurogenesis. Apical constriction depends on actomyosin contractility downstream of the Hedgehog (Hh) and bone morphogenetic protein (BMP) pathways. We identify a role for integrin adhesion receptors in MF progression. We show that Hh and BMP regulate integrin expression, the loss of which disrupts apical constriction and slows furrow progression; conversely, elevated integrins accelerate furrow progression. We present evidence that integrins regulate MF progression by promoting microtubule stabilization, since reducing microtubule stability rescues integrin-mediated furrow acceleration. Thus, integrins act as a genetic link between tissue-level signaling events and morphological change at the cellular level, leading to morphogenesis and neurogenesis in the eye.
在形态发生过程中，细胞外信号触发细胞亚群中的肌动球蛋白收缩，以协调细胞形状的变化。为了阐明信号介导的组织模式形成与细胞骨架重塑之间的联系，我们研究了形态发生沟（MF）的进展，这是一种顶端收缩波，在光感受器神经发生之前穿过果蝇眼成虫盘。顶端收缩取决于刺猬信号通路（Hh）和骨形态发生蛋白（BMP）通路下游的肌动球蛋白收缩。我们确定了整合素黏附受体在MF进展中的作用。我们表明，Hh和BMP调节整合素表达，整合素表达的缺失会破坏顶端收缩并减缓沟的进展；相反，整合素水平升高会加速沟的进展。我们提供证据表明，整合素通过促进微管稳定来调节MF进展，因为降低微管稳定性可挽救整合素介导的沟加速。因此，整合素作为组织水平信号事件与细胞水平形态变化之间的遗传联系，导致眼睛的形态发生和神经发生。
