23172
From Cortical Development to Cortex in the Dish: Modeling Human Neurodevelopmental Disease
Brain imaging approaches have allowed for a low-resolution understanding of network abnormalities in living human brains of patients with neurodevelopmental and neuropsychiatric disorders, however a deeper understanding of pathologies affecting neural network behavior are only possible when abnormalities in cell connectivity, network activity and transcriptomes can be directly interrogated and correlated in an experimental system amenable to manipulation, phenotyping and high-throughput analysis.
Objectives:
We aim to generate a high-throughput in vitro model of the human developing brain to investigate the effect of disease-linked mutations on brain development and circuit function.
Methods:
I will present recent work on the development and long-term culture of 3D cerebral organoids derived from human pluripotent stem cells. This will include analysis of the developmental trajectory, cellular diversity and neuronal network features that mature within this human brain organoid model.
Results:
I will show that phenotypic abnormalities observed in patients carrying genetic mutations linked to neurodevelopmental disease can be reproduced within cerebral organoids.
Conclusions:
The work provides initial proof-of-principle demonstration that selected aspects of human neurodevelopmental disease can be modeled in high-throughput using 3D cerebral organoids.