Developmental scaling of cell mechanosensitivity in epithelial tissue
All biological systems tailor their organization and properties to their size. Such size scaling is essential to The scaling of biological structures and substructures with their size is a preeminent and essential feature of life....
All biological systems tailor their organization and properties to their size. Such size scaling is essential to The scaling of biological structures and substructures with their size is a preeminent and essential feature of life. Accordingly, the study of scaling properties had a profound impact on our understanding of animal physiology, gene expression, cell cycle regulation and intracellular dynamics. Their study at the cell level has often led to the discovery of the fundamental mechanisms allowing cells to probe their size or geometry (cell size ruler). Yet we are very far from understanding how such cell size ruler controls more macroscopic processes such as morphogenesis or global tissue size. Building on interdisciplinary methods (live-imaging, genetics, physical modeling, transcriptomics) and on the recent progresses in mechanical force sensing, we aim to understand how cell size rulers are generated in epithelial tissues and how they are modulating in time to account for the spatiotemporal regulation morphogenesis and proliferation of developing organism. More specifically, working from the cell to the tissue levels, we explore how the interplay between two fundamental and prevalent structures, actomyosin stress fibers and tricellular junctions, define an internal cell ruler probing cell size in the control of epithelial morphogenesis, signalling and proliferation. Conversely, we will explore how systemic hormonal or local tissue timers modulate such internal cell rulers to control the temporal regulation of tissue dynamics. Thereby we will understand how tissue and organismal level regulation could impact on cell size rules to control the temporal dynamics of tissues. By focusing on both the genetic and mechanical regulation at different length-scales (cytoskeleton, cell, and tissue) and time-scales (seconds to hours), we expect to provide novel and fundamental insights into the spatiotemporal mechanisms governing the dynamics of biological structures.ver más
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