Mechanobiological Analysis of Microtubule-Based Forcesat Epithelial Adherens Junctions During Tissue Morphogenesis

力学生物学是研究源自生物分子的力的时空组织，在调节多种细胞行为中起着重要作用。其中一个例子是组织形态发生，单个细胞自组装成具有高度特化形式和功能的复杂组织和器官。这种精确的雕刻需要应用细胞骨架在细胞内产生的力，并通过邻近细胞内和细胞之间的粘附分子传递这些力。为了重塑组织，力产生必须超过机械阻力，因此力产生和组织刚度的整体模式共同决定了组织重排的速度和方向。在分子水平上，遗传过程控制着发育组织内的力量产生和组织刚度。虽然已经确定了许多在形态发生过程中调节这些过程的基因和化学线索，但对发育组织中这些机械过程如何在细胞间耦合的定量知之甚少。在这里，我们将使用新的光学和化学工具结合经典的遗传方法来定量分析细胞骨架在组织中形态发生重排过程中如何协调跨细胞的力。考虑到它们作为全球力整合器的新兴作用，研究的一个特别重点将放在微管（MTs）在粘附连接处的作用上。

Mechanobiology, the spatio-temporal organization of forces originating from biomolecules, plays an important role in regulating a variety of cellular behaviors. One such example is tissue morphogenesis, where individual cells self-assemble into complex tissues and organs with highly specialized forms and functions. Such precise sculpting requires the application of forces generated within cells by the cytoskeleton and transmission of these forces through adhesion molecules within and between neighboring cells. In order to reshape a tissue, force generation must exceed mechanical resistance, thus global patterns of force generation and tissue stiffness jointly dictate speed and direction of tissue rearrangements. On the molecular level, genetic processes control both, force production and tissue stiffness within the developing tissue. While many of the genes and chemical cues that regulate these processes during morphogenesis have been identified, little is known quantitatively about how these mechanical processes are coupled across cells in a developing tissue. Here, we will use new optical and chemical tools in conjunction with classical genetic approaches to quantitatively analyze how the cytoskeleton coordinates forces across cells during morphogenetic rearrangements in a tissue. Considering their emerging role as global force integrators, a particular focus of the study will be put on the role of microtubules (MTs) nucleated at adherens junctions.