How do epithelial tissues acquire their shape?

Epithelia are the most abundant tissue type in the animal body. Epithelia not only define and regulate body compartments, but also undergo dynamic remodeling during embryonic development to shape animal bodies. The specific arrangement and morphology of epithelial cells are intricately adapted to meet the physiological demands of the unique tissue environment. All epithelia are composed of confluent sheets of cells with a shared polarity axis. However, the architectural diversity of epithelial tissues is striking, and tissues can transition between different forms during development. The biological and mechanical factors driving these architectural variations remain poorly understood.



This prompted us to ask to what extent epithelial architecture emerges from two mechanical considerations: A) the constraints of densification and B) cell-cell adhesion, a hallmark feature of epithelial cells. To address these questions, we developed a novel polyline cell-based computational model and used it to make theoretical predictions about epithelial architecture upon changes to density and cell-cell adhesion. We tested these predictions using cultured cell experiments. Our results show that the appearance of extended lateral cell-cell borders in culture arises as a consequence of crowding–independent of cell-cell adhesion. However, cadherin-mediated cell-cell adhesion is associated with a novel architectural transition. Our results suggest that this transition represents the initial appearance of a distinctive epithelial architecture. Together our work reveals the distinct mechanical roles of densification and adhesion to epithelial layer formation and provides a novel theoretical framework to understand the less well-studied apical-basal plane of epithelial tissues.