Exploring the role of mechanical forces on human cortex development using organoid models

Neural organoids from human pluripotent stem cells are capable of self-organization but fail to recapitulate cellular identities and the structure of the mature brain. Grown on passive scaffolds, they fail to reproduce active mechanical forces that are crucial during in vivo development. Recent studies in the Ranga lab have shown that stretching human neural tube organoids, during a critical time frame, enhances the efficiency of floor plate patterning, a crucial event during the early stages of neurogenesis. Building on these results, we aim to develop processes for the in-plane, active stretching of human neural organoids to investigate the role of mechanical forces in enhancing cellular diversity, patterning and maturation in engineered neural tissues. We plan to generate a developmental atlas of actuated organoids with enhanced dorso-ventral patterning in the hindbrain, as well as cortical layering in the cortex. Furthermore, cellular diversity will be mapped to dynamic mechanical forces and functional electrical activity. This project will contribute to uncovering the role of biomechanics in later stages of the human neurodevelopment and have the potential to generate more complex and well-organized neural organoid models.