Investigating how mechanical connectivity yields developmental robustness

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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.