Human brain development is prolonged and uniquely vulnerable: Although neurogenesis begins during embryogenesis, maturation processes such as synaptogenesis, myelination, and circuit refinement continue into early adulthood, shaping the mature brain. This extended window increases the brain's vulnerability to various genetic and environmental disruptions. Even subtle early disturbances can derail brain development trajectories, leading to neurodevelopmental disorders (NDDs) with irreversible, lifelong effects, highlighting a key challenge: determining when, where, and how early insults lead development toward pathology.
Human brain organoids have become powerful three-dimensional in vitro models derived from pluripotent stem cells that self-organize into structures mimicking early brain development. These include the organization of ventricular zone-like (VZ) and cortical progenitor populations, as well as primitive neuronal layers, offering insights into the cellular processes behind human
corticogenesis. Brain organoids provide a way to study mechanisms of human brain development and to model neurodevelopmental disorders that are challenging to examine in vivo due to limited tissue access and species differences in developmental pathways. When derived from patientspecific iPSCs, brain organoids have uncovered previously unknown cellular mechanisms involved in congenital malformations such as microcephaly, lissencephaly, and heterotopia. Besides, human brain organoids have also emerged as a novel and innovative experimental system to study and model devastating brain tumors such as glioblastoma.
The summer school training is intended to provide an introduction to human brain organoids and their applications to decoding human brain developmental and disease mechanisms, using specific neurogenetic diseases and glioblastoma as examples.