618B Poster - 08. Patterning, morphogenesis and organogenesis
Friday April 08, 2:00 PM - 4:00 PM
Quantiative Models of Mechanical Feedback in Morphogenesis
Authors: Nikolas Claussen 1; Matthew Lefebvre 1; Hannah Gustavson 1; Noah Mitchell 1; Stefano De Renzis 2; Boris Shraiman 1; Sebastian Streichan 1
Affiliations: 1) University of California, Santa Barbara; 2) European Molecular Biology Laboratory, Heidelberg
Keywords: w. biomechanical forces; x. computational models
Morphogenesis is an inherently dynamic process which bridges cellular and tissue scales. Quantitative analysis and mathematical modelling applied to dynamic imaging data can play a crucial role in elucidating developmental processes and can turn biological hypotheses into quantitative, testable predictions. The actomyosin cytoskeleton plays a central role in sculpting the developing embryo across metazoans, yet the mechanisms by which it is controlled are poorly understood. Recent evidence suggests that the cytoskeleton can dynamically respond to mechanical stimuli. Yet distinguishing which behaviors are key signatures of such mechanical feedback has proven difficult. In D. melanogaster body axis elongation, a canonical example of convergent extension, non-muscle myosin II (MyoII) is recruited anisotropically to cell-cell junctions where it generates force. But how the cytoskeleton is oriented remains incompletely understood.
We show how simple, physical models with a small number of biologically meaningful parameters allow us to describe the behavior of MyoII expected if the cytoskeleton responds to mechanical signals and test our conjectures using an \emph{in-toto} characterization of MyoII. We can quantitatively predict the dynamics of both the magnitude and orientation of junctional MyoII based on mechanical cues, cell deformation rates and embryo geometry. We find excellent agreement with experimental data in both wild-type embryos and when using genetic and optogenetic perturbations. Our results show how mathematical models can rationalize morphogenetic behaviors and uncover mechanisms to be targeted by molecular investigations. We add a novel perspective on developmental biology: morphogenesis may be organized by mechanical and geometric signals without constant input of genetic patterning, allowing for robust, modular and self-organized processes.