北畑 裕之

Epithelia consist of proliferating and differentiating cells that often display patterned arrangements. However, the mechanism regulating these spatial arrangements remains unclear. Here, we show that cell-cell adhesion dictates multicellular patterning in stratified epithelia. When cultured keratinocytes, a type of epithelial cell in the skin, are subjected to starvation, they spontaneously develop a pattern characterized by areas of high and low cell density. Pharmacological and knockout experiments show that adherens junctions are essential for patterning, whereas the mathematical model that only considers local cell-cell adhesion as a source of attractive interactions can form regions with high/low cell density. This phenomenon, called cell-cell adhesion-induced patterning (CAIP), influences cell differentiation and proliferation through Yes-associated protein modulation. Starvation, which induces CAIP, enhances the stratification of the epithelia. These findings highlight the intrinsic self-organizing property of epithelial cells.

Abstract The mechanism of self-propelled particle motion has attracted much interest in mathematical and physical understanding of the locomotion of living organisms. In a top-down approach, simple time-evolution equations are suitable for qualitatively analyzing the transition between the different types of solutions and the influence of the intrinsic symmetry of systems despite failing to quantitatively reproduce the phenomena. We aim to rigorously show the existence of the rotational, oscillatory, and quasi-periodic solutions and determine their stabilities regarding a canonical equation proposed by Koyano et al. (J Chem Phys 143(1):014117, 2015) for a self-propelled particle confined by a parabolic potential. In the proof, the original equation is reduced to a lower dimensional dynamical system by applying Fenichel’s theorem on the persistence of normally hyperbolic invariant manifolds and the averaging method. Furthermore, the averaged system is identified with essentially a one-dimensional equation because the original equation is O(2)-symmetric.