Mechanical control of anisotropic tissue growth and oriented cell divisions

Morphogenesis of developing tissues is achieved by anisotropic growth, wherein the tissue expands unevenly in different directions, resulting in an anisotropic organ shape. Anisotropic growth requires directed cell divisions, which could be influenced by intrinsic or extrinsic forces acting on the tissue. However, the mechanisms through which mechanical forces govern anisotropic tissue growth are not well understood. Here we propose a cell-level model for anisotropic growth based on mechanical feedback between cell motility, mechanical pressure, and division rates. Our model builds upon cellular vertex models by incorporating cell polarity and cell cycle dynamics, cell growth and division, and contact inhibition of proliferation. Our findings underscore the critical role of contact inhibition, cell polarity alignment and cell elasticity in governing tissue growth patterns. Specifically, alignment of cell polarity can induce symmetry breaking during growth, resulting from the anisotropic distribution of mechanical pressure. Notably, polarity axis defines the direction of tissue growth: in regions experiencing lower compression at the tissue rear, there is a higher frequency of cell divisions, while in regions under greater compression at the front, cell divisions tend to be less frequent. We show that the extent of division anisotropy can be manipulated by adjusting cell area elasticity and motility parameters, thus elucidating the design principles for anisotropic morphogenesis.