Three-dimensional Cell and Nuclear Geometries Inform Tissue Level Fluid Mechanics During Epithelial Remodeling

Abstract

During epithelial remodeling, mechanical and molecular programs must coordinate to drive the cell shape changes that enable new tissue topologies. Dynamic morphogenesis requires epithelia to preferentially exhibit solid- or fluidlike properties depending on developmental and biophysical constraints. Convergent extension in the Drosophila germband epithelium is one such remodeling event, during which the lateral ectoderm lengthens by two-fold along the primary body axis while concomitantly shortening orthogonally. This process is an incredibly dynamic and attractable system for studying tissue morphogenesis mechanics in vivo. Germband extension is driven by oriented cell intercalation through T1 transitions, where cells directionally interdigitate with one another through stereotyped junctional remodeling. In chapter 1, we show that contractile events produce a continuous “rectification” of cell contacts, in which interfaces systematically rotate toward more vertical orientations. As interfaces rotate, their behavior transitions from elongating to contractile regimes, indicating that planar polarized interface identities are continuously re-interpreted in time depending on orientation angle. Rotating interfaces acquire higher levels of Myosin II as they become more vertical, while disruptions to the contractile molecular machinery reduce the rates of rotation. Through this angle rectification, the available pool of vertical interfaces is continuously replenished as new interfaces acquire a contractile identity through rotation, allowing cells to participate in multiple staggered rounds of intercalation. In foams and colloidal glasses, component grain size influences material mechanics; in chapter 2, we analogously investigate how cell and nuclear size affect tissue mechanics. mh mutant embryos have doubled cell densities, creating cells with altered 3D aspect ratios. Nuclei scale nonlinearly with cells, possessing rounder shapes and reduced apical-basal heights. These compacted nuclei mechanically jam the tissue, disrupting fluidization and impairing convergent extension movements. Interestingly, oscillatory amplitudes and frequencies in mh cells are comparable to control despite their reduced size, demonstrating an uncoupling between biochemical oscillation machinery and cell dimensions. Additionally, though planar-polarized magnitudes are dampened, the angular assignment of contractile interface behaviors is preserved, suggesting the planar informational system still operates with high fidelity despite reduced cell dimensions. These results suggest that development has fine-tuned epithelial dimensions to work at time-scales compatible with embryonic requirements.