Buckling without Bending: A New Paradigm in Morphogenesis

Abstract

A curious feature of organ and organoid morphogenesis is that in certain cases, spatial oscillations in the thickness of the growing “film” are out of phase with the deformation of the slower-growing “substrate,” while in other cases, the oscillations are in phase. The former cannot be explained by elastic bilayer instability, and contradict the notion that there is a universal mechanism by which brains, intestines, teeth, and other organs develop surface wrinkles and folds. Inspired by the microstructure of the embryonic cerebellum, we develop a new model of 2D morphogenesis in which system-spanning elastic fibers endow the organ with a preferred radius, while a separate fiber network resides in the otherwise fluidlike film at the outer edge of the organ and resists thickness gradients thereof. The tendency of the film to uniformly thicken or thin is described via a “growth potential.” Several features of cerebellum, +blebbistatin organoid, and retinal fovea morphogenesis, including out-of-phase behavior and a film thickness amplitude that is comparable to the radius amplitude, are readily explained by our simple analytical model, as may be an observed scale invariance in the number of folds in the cerebellum. We also study a nonlinear variant of the model, propose further biological and bioinspired applications, and address how our model is and is not unique to the developing nervous system.