Speaker
Description
Human neurodevelopmental disorders often originate from disruptions during early cortical development. This motivates the use of brain organoids which provide an experimental platform that recapitulates key aspects of human neurogenesis. However, brain organoid exhibit substantial variability in developmental dynamics due to intrinsic cellular heterogeneity. Although mathematical models have been proposed to study organoid growth, few approaches explain how complex developmental dynamics emerge from simple cellular rules. Here, we develop an agent-based model of brain organoid development in which radial glial cells, intermediate progenitors, and neurons interact through minimal rules governing minimal rules governing proliferation, differentiation, migration, cell–cell signaling, and the temporal regulation of division modes. By systematically perturbing these rules in silico, we investigate which mechanisms are necessary to reproduce characteristic organoid growth dynamics. The model further provides a framework to explore how disruptions in progenitor behavior may lead to neurodevelopmental disorders such as ASPM-associated microcephaly.
