Biological systems tailor their properties and behavior to their size throughout development and in numerous aspects of physiology. However, such size scaling remains poorly understood as it applies to cell mechanics and mechanosensing. By examining how the Drosophila pupal dorsal thorax epithelium responds to morphogenetic forces, we found that the number of apical stress fibers (aSFs) anchored to adherens junctions scales with cell apical area to limit larger cell elongation under mechanical stress. aSFs cluster Hippo pathway components, thereby scaling Hippo signaling and proliferation with area. This scaling is promoted by tricellular junctions mediating an increase in aSF nucleation rate and lifetime in larger cells. Development, homeostasis, and repair entail epithelial cell size changes driven by mechanical forces; our work highlights how, in turn, mechanosensitivity scales with cell size.

Small cell clusters exhibit numerous phenomena typically associated with complex systems, such as division of labour and programmed cell death. A conserved class of such clusters occurs during oogenesis in the form of germline cysts that give rise to oocytes. Germline cysts form through cell divisions with incomplete cytokinesis, leaving cells intimately connected through intercellular bridges that facilitate cyst generation, cell fate determination and collective growth dynamics. Using the well-characterized Drosophila melanogaster female germline cyst as a foundation, we present mathematical models rooted in the dynamics of cell cycle proteins and their interactions to explain the generation of germline cell lineage trees (CLTs) and highlight the diversity of observed CLT sizes and topologies across species. We analyse competing models of symmetry breaking in CLTs to rationalize the observed dynamics and robustness of oocyte fate specification, and highlight remaining gaps in knowledge. We also explore how CLT topology affects cell cycle dynamics and synchronization and highlight mechanisms of intercellular coupling that underlie the observed collective growth patterns during oogenesis. Throughout, we point to similarities across organisms that warrant further investigation and comment on the extent to which experimental and theoretical findings made in model systems extend to other species.

The outer epithelial layer of zebrafish retinae contains a crystalline array of cone photoreceptors, called the cone mosaic. As this mosaic grows by mitotic addition of new photoreceptors at the rim of the hemispheric retina, topological defects, called “Y-Junctions”, form to maintain approximately constant cell spacing. The generation of topological defects due to growth on a curved surface is a distinct feature of the cone mosaic not seen in other well-studied biological patterns like the R8 photoreceptor array in the Drosophila compound eye. Since defects can provide insight into cell-cell interactions responsible for pattern formation, here we characterize the arrangement of cones in individual Y-Junction cores as well as the spatial distribution of Y-junctions across entire retinae. We find that for individual Y-junctions, the distribution of cones near the core corresponds closely to structures observed in physical crystals. In addition, Y-Junctions are organized into lines, called grain boundaries, from the retinal center to the periphery. In physical crystals, regardless of the initial distribution of defects, defects can coalesce into grain boundaries via the mobility of individual particles. By imaging in live fish, we demonstrate that grain boundaries in the cone mosaic instead appear during initial mosaic formation, without requiring defect motion. Motivated by this observation, we show that a computational model of repulsive cell-cell interactions generates a mosaic with grain boundaries. In contrast to paradigmatic models of fate specification in mostly motionless cell packings, this finding emphasizes the role of cell motion, guided by cell-cell interactions during differentiation, in forming biological crystals. Such a route to the formation of regular patterns may be especially valuable in situations, like growth on a curved surface, where the resulting long-ranged, elastic, effective interactions between defects can help to group them into grain boundaries.

Studies of fate patterning during development typically emphasize cell-cell communication via diffusible signals. Recent experiments on monolayer stem cell colonies, however, suggest that mechanical forces between cells may also play a role. These findings inspire a model of mechanical patterning: fate affects cell contractility, and pressure in the cell layer biases fate. Cells at the colony boundary, more contractile than cells at the center, seed a pattern that propagates via force transmission. In agreement with previous observations, our model implies that the width of the outer fate domain depends only weakly on colony diameter. We further predict and confirm experimentally that this same width varies non-monotonically with substrate stiffness. This finding supports the idea that mechanical stress can mediate patterning in a manner similar to a morphogen; we argue that a similar dependence on substrate stiffness can be achieved by a chemical signal only if strong constraints on the signaling pathway’s mechanobiology are met.