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

力学生物学是由生物分子产生的力的时空组织，在调节多种细胞行为方面发挥着重要作用。一个这样的例子是组织形态发生，即单个细胞自我组装成具有高度专门化形式和功能的复杂组织和器官。这种精确的雕刻需要施加细胞骨架在细胞内产生的力，并通过相邻细胞内和相邻细胞之间的黏附分子传递这些力。为了重塑组织，力的产生必须超过机械阻力，因此力产生的整体模式和组织的硬度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中的组织中的力量生产和组织硬度。虽然在形态发生过程中调节这些过程的许多基因和化学线索已经被识别出来，但对于这些机械过程是如何在发育中的组织中跨细胞耦合的，我们知之甚少。在这里，我们将使用新的光学和化学工具结合经典的遗传学方法来定量分析细胞骨架如何在组织的形态发生重排过程中协调细胞间的力。考虑到它们作为全球力集成器的新角色，本研究的重点将放在附着结合处成核的微管(MT)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.