Brain Folds and the Extracellular Matrix: Lessons from Brain Organoids*

Neurodevelopmental brain disorders include a spectrum of diseases, ranging from brain malformations, such as microcephaly (small brain) and lissencephaly (smooth brain), through different forms of epilepsy, to intellectual disability, autism spectrum disorders, and schizophrenia. Our studies focused on haploinsufficient mutations in LIS1 that result in lissencephaly. Using different brain organoid models, we detected changes in the matrisome, which includes components of the extracellular matrix (ECM) and their modulating enzymes. We identified the molecular mechanisms involved in changing gene expression and demonstrated how the physical properties of the organoids change. We believe that our studies are important for understanding how the brain folds during embryonic development and what goes wrong in case of diseases.