Large-scale cortex-core structure formation in brain organoids

Abstract

Brain organoids recapitulate a number of brain properties, including neuronal diversity. However, do they recapitulate brain structure? Using a hydrodynamic description for cell nuclei as particles interacting initially via an effective, attractive force as mediated by the respective, surrounding cytoskeletons, we quantify structure development in brain organoids to determine what physical mechanism regulates the number of cortex-core structures. Regions of cell nuclei overdensity in the linear regime drive the initial seeding for cortex-core structures, which ultimately develop in the non-linear regime, as inferred by the emergent form of an effective interaction between cell nuclei and with the extracellular environment, as mediated by a dynamic cytoskeleton. Individual cortex-core structures then provide a basis upon which we build an extended version of the buckling without bending morphogenesis (BWBM) model, with its proliferating cortex and constraining core, to predict foliations/folds of the cortex in the presence of a nonlinearity due to cortical cells actively regulating strain. In doing so, we obtain asymmetric foliations/folds with respect to the trough (sulci) and the crest (gyri). In addition to laying new groundwork for the design of more familiar and less familiar brain structures, the hydrodynamic description for cell nuclei during the initial stages of brain organoid development provides an intriguing quantitative connection with large-scale structure formation in the universe.