Investigating how mechanical connectivity yields developmental robustness

摘要 关键的形态发生过程的可重复发生对生物体的命运至关重要， 在组织损伤或环境扰动下。虽然我们对基因冗余和 调控实现了稳健的发展，但对组织如何机械地确保 扰动时可再现的形状变化。这个项目揭示了人口的身体相互作用 细胞对挑战性条件做出机械反应，并修改它们的集体行为， 正确的最终形状。 细胞协调组织规模的力和运动的一种方式是通过直接的机械 连接.事实上，许多发育中的组织表现出肌动球蛋白连接的细胞外网络， 连接数百个细胞。一个很大的障碍是亚细胞成像和定量的挑战。 蛋白质在组织中的比例。我采用了最初用于追踪高噪声的拓扑平滑算法 丝状结构的星系在宇宙中的数据，以跟踪高噪音丝状肌球蛋白结构， 共焦图像。这使得第一次定量的超细胞肌球蛋白网络在整个 在发育过程中。随后的分析采用了网络理论的技术，使我能够 确定果蝇果蝇胚胎在腹沟形成期间的稳健折叠是机械的， 由其腹侧细胞上的超细胞网络模式所确保。 新发现的超细胞网络在协调强大的形状变化方面的重要性 强调需要全面了解超细胞网络是如何形成的，以及它们是如何形成的。 图案影响细胞群的功能和鲁棒性。在组织水平上破译鲁棒性， 其中必须考虑数百个细胞的位移和命运，需要界面技术 细胞和发育生物学、生物物理学和计算机科学。拟议的项目将采取高度 跨学科的方法，以确定如何超细胞网络模式的控制分子，在细胞 水平，并通过组织约束。同样，组织水平模式的异质性如何影响形态发生 鲁棒性将得到解决。这种对超细胞的结构和功能的全面研究， 网络将代表一种解释不同发育组织机械鲁棒性的新方法。作为 那么，机械鲁棒性的一般化描述有可能揭示新的预测路径， 控制组织畸形，这将代表发育生物学和 胎儿医学

ABSTRACT It is essential for the fate of an organism that key morphogenetic processes occur reproducibly even under tissue damage or environmental perturbations. While much is known about how genetic redundancy and regulation achieves robust development, less is understood about how a tissue mechanically ensures reproducible shape change when perturbed. This project uncovers how populations of physically interacting cells mechanically respond to challenging conditions and modify their collective behavior to still sculpt the correct final shape. One way for cells to coordinate tissue-scale forces and movements is through direct mechanical connections. In fact, many developing tissues exhibit supracellular networks of actomyosin connections that link hundreds of cells. A large roadblock has been with the challenges of imaging and quantifying subcellular protein at the tissue scale. I adapted a topological smoothing algorithm originally used to trace high-noise filamentous structure of galaxies in the Universe to data to trace high-noise filamentous myosin structure in confocal images. This allowed for the first quantification of a supracellular myosin network across an entire tissue over developmental time. Subsequent analysis adopting techniques from network theory allowed me to identify that the robust folding of the Drosophila fruit fly embryo during ventral furrow formation is mechanically ensured by patterns in the supracellular network spanning its ventral cells. This newly discovered importance of supracellular networks in coordinating robust shape change highlights the need for a comprehensive understanding of how supracellular networks form, and how their patterns impact the function and robustness of a population of cells. Deciphering robustness at the tissue-level, where the displacement and fate of hundreds of cells must be considered, requires techniques at the interface of cell and developmental biology, biophysics and computer science. The proposed project will take a highly interdisciplinary approach to identify how supracellular network patterns are controlled molecularly, at the cell level, and via tissue constraints. As well, how heterogeneity in tissue-level patterns impacts morphogenetic robustness will be addressed. Together this comprehensive study of the structure and function of supracellular networks will represent a new way to interpret mechanical robustness across diverse developing tissues. As well, a generalized description of mechanical robustness has the potential to uncover new paths to predict and control tissue malformation, which would represent a significant advance for both developmental biology and fetal medicine.