Many animal embryos pull and close an epithelial sheet around the ellipsoidal egg surface during a gastrulation process known as epiboly. The ovoidal geometry dictates that the epithelial sheet first expands and subsequently compacts. Moreover, the spreading epithelium is mechanically stressed and this stress needs to be released. Here we show that during extraembryonic tissue (serosa) epiboly in the insect Tribolium castaneum, the non-proliferative serosa becomes regionalized into a solid-like dorsal region with larger non-rearranging cells, and a more fluid-like ventral region surrounding the leading edge with smaller cells undergoing intercalations. Our results suggest that a heterogeneous actomyosin cable contributes to the fluidization of the leading edge by driving sequential eviction and intercalation of individual cells away from the serosa margin. Since this developmental solution utilized during epiboly resembles the mechanism of wound healing, we propose actomyosin cable-driven local tissue fluidization as a conserved morphogenetic module for closure of epithelial gaps.

The cephalic furrow is a deep epithelial fold that demarcates the head–trunk boundary of fly embryos during gastrulation. It forms under strict genetic control using active cellular mechanisms and follows an invariant morphogenetic sequence. But unlike other embryonic invaginations, the cells that invaginate in the cephalic furrow do not give rise to any precursor tissues or larval traits. The cephalic furrow is transient and unfolds leaving no trace. For these reasons, its function during development has remained elusive. Here we show that the cephalic furrow plays a mechanical role duringDrosophilagastrulation. By live-imaging mutant embryos, we find that without the cephalic furrow, ectopic folds appear around the head–trunk interface indicating that the epithelial stability has been compromised. Usingin vivoperturbations andin silicosimulations, we demonstrate that ectopic folding in cephalic furrow mutants occurs due to the concomitant formation of mitotic domains and extension of the germ band. These events increase the tissue strain in the head–trunk interface giving rise to mechanical instabilities. Further, we show by simulations that an early pre-patterned invagination can effectively prevent the build-up of compressive stresses by retaining epithelial tissue out-of-plane before other morphogenetic movements take place. Our findings suggest the cephalic furrow absorbs compressive stresses at the head–trunk boundary during fly gastrulation, and raise the hypothesis that mechanical forces may have played a role in the evolution of the cephalic furrow.

Cell migration has been a subject of study in a broad variety of biological systems, from morphogenetic events during development to cancer progression. In this work, we describe single-cell movement in a modular framework from which we simulate the collective behavior of glioblastoma cells, the most prevalent and malignant primary brain tumor. We used the U87 cell line, which can be grown as a monolayer or spatially closely packed and organized in 3D structures called spheroids. Our integrative model considers the most relevant mechanisms involved in cell migration: chemotaxis of attractant factor, mechanical interactions and random movement. The effect of each mechanism is integrated into the overall probability of the cells to move in a particular direction, in an automaton-like approach. Our simulations fit and reproduced the emergent behavior of the spheroids in a set of migration assays where single-cell trajectories were tracked. We also predicted the effect of migration inhibition on the colonies from simple experimental characterization of single treated cell tracks. The development of tools that allow complementing molecular knowledge in migratory cell behavior is relevant for understanding essential cellular processes, both physiological (such as organ formation, tissue regeneration among others) and pathological perspectives. Overall, this is a versatile tool that has been proven to predict individual and collective behavior in U87 cells, but that can be applied to a broad variety of scenarios.