Impact of environmental asymmetry on epithelial morphogenesis

Epithelial folding is a universal biological phenomenon in morphogenesis, typical examples being brain gyri, villi of the intestinal tract, and imaginal discs in invertebrates. During epithelial morphogenesis, the physical constraints imposed by the surrounding microenvironment on epithelial tissue play critical roles in folding morphology. In this study, we focused on the asymmetry of the environmental constraints sandwiching the epithelial sheet and introduced the degree of asymmetry, which indicates whether the basal or apical side of the epithelium is closer to the constraint wall. Then, we investigated the relationship between the degree of asymmetry and epithelial folding morphology using three-dimensional vertex simulations. The results show that the folding patterns of the epithelial sheets change from spot patterns to labyrinth patterns and then to hole patterns as the degree of asymmetry changes. Furthermore, we examined the pattern formation in terms of the equation of out-of-plane displacement of the sheet derived from the mechanical energy functional.