Intestinal villi are tiny, finger-like projections in our small intestine. Each villus is covered by a monolayer of epithelial cells, known as enterocytes, which are essential for both digestion and defense. Thus, it is crucial to understand how the monolayer architecture is controlled by the cellular junctional forces. Here, we focus on an epithelial junctional protein NMII (nonmuscle myosin II) within mouse villi epithelia, specifically one of its isoforms, NMIIC, which is responsible for mediating junctional forces and tissue patterning. Loss of NMIIC disrupts tissue architecture, leading to irregular cell shapes and jagged cell boundaries, indicative of altered junctional forces regulated by NMIIC. The NMIIC proteins are organized in a periodic puncta-like manner along the cell-cell junctional line and help maintain a regular epithelial morphology. Experiments reveal that in the absence of NMIIC, these cells recruit another isoform NMIIA puncta along cell periphery which significantly alters the tissue organization, suggesting a substantial change in junctional forces. In order to understand the roles of the junctional proteins in maintaining tissue morphology, we developed a two-dimensional active force-based model of tissue monolayers, where each cell is a soft deformable object made of beads and springs. The beads serve a coarse-grained representation of the NMII puncta across the cell periphery. Our model reveals that the increasing bead number or decreasing spring-strength results in irregular tissue morphology with long tailed shape index distribution and curved cell edges as seen in experiments—finally, our model makes other predictions that can be tested in experiments, such as increasing bead number will lead to a decrease in the overall tissue tension. Our results and simulation framework offer potential mechanistic insights that may open up new avenues in developmental biology and physiology.
Ray et al. (Sun,) studied this question.