In multicellular organisms, cells adopt various shapes, from flattened sheets of endothelium to dendritic neurons, that allow the cells to function effectively. Here, we elucidated the unique shape of cells in the stratified epithelia of the epidermis that allows them to achieve homeostasis of the tight junction (TJ) barrier. Using intimate in vivo 3D imaging, we found that the basic shape of
TJ-bearing cells is a flattened Kelvin’s tetrakaidecahedron
(f-TKD), an optimal shape for filling space. In vivo live imaging further elucidated the dynamic replacement of TJs on the edges of f-TKD cells that enables the TJ-bearing cells to translocate across the TJ barrier. We propose a spatiotemporal orchestration
model of f-TKD cell turnover, where in the classic context of “form follows function,” cell shape provides a fundamental basis for the barrier homeostasis and physical strength of cornified stratified epithelia.