Coordination of ventral furrow formation during Drosophila gastrulation through mechanical stress feedback
Holcomb, Michael C.
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The work presented in this dissertation seeks to answer the following overarching question: how do cells harmonize their activities to collectively produce organism-level restructuring and rearrangements of tissues? One well-studied example of this kind of restructuring is ventral furrow formation (VFF), which occurs during a process known as gastrulation in the Drosophila melanogaster embryo. During VFF a band of cells on the underside of the embryo, known as the mesoderm primordium, becomes internalized. This is accomplished by individual cells undergoing apical constrictions that collectively produce enough tension across the outer (apical) surface to buckle the cell-layer inwards. The importance of proper gene expression for this inherently mechanical process is well established; however, how cells coordinate their individual shape changes into a tissue-level generation of spontaneous curvature is an open question. The hypothesis of this dissertation is that this intercellular coordination is accomplished through cells monitoring the underlying mechanical stress field and engaging in mechanical stress feedback. To test this hypothesis, two complementary two-dimensional models and one in-development three-dimensional model are presented. Cells in all three models are represented as mechanically excitable objects that interact with each other through pairwise potentials. The first two-dimensional model focuses on the transverse cross-section of the Drosophila embryo and faithfully reproduces the process of VFF with a system of mechanically active cells that are coordinating shape changes through mechanical stress feedback. The second two-dimensional model considers the apical surface of the embryo and identifies how cells of the mesoderm primordium coordinate the progression of apical constrictions through sensitivity to tensile mechanical stress. The in-development three-dimensional model seeks to combine aspects of both two-dimensional models and is presented with preliminary results. In addition to modeling, a means of experimental verification using high resolution confocal microscopy images of the underside of the Drosophila embryo was pursued. A statistical comparison between averaged live embryo data and the two-dimensional surface model affirm that the apical constriction of cells in the mesoderm primordium is likely coordinated via tensile mechanical stress. Both regional and cellular coordination is shown to be imperative for proper VFF and it is found that tensile stress sensitivity is likely to contribute positively to the robustness of a system. All together, the results presented in this dissertation provide compelling evidence that the global coordination required for successful VFF in the Drosophila melanogaster embryo is accomplished through tissue-level mechanical stress feedback.