Eyal Karzbrun, will present seminar. Hosted by: Itai Cohen.
Seminar Title: Wrinkling of Human Brain Organoids on a Chip Driven by Mechanical Instabilities
Abstract: The origin of human brain wrinkling remains an open fundamental problem, with implications to neurodevelopmental disorders. Physical studies in polymer gel models suggest wrinkling emerge spontaneously due to development of compression forces during differential growth of cell layers, however biological evidence is limited. Here, we report the emergence of surface wrinkles during in vitro development of human brain organoids, in a micro-fabricated compartment, which supports in situ imaging at subcellular resolution over weeks. The folding dynamics and morphology exhibit similarity to folding in vivo. By studying the cellular dynamics, we observe nuclei compression during development, and the emergence of convolutions at a critical cell density. We identify two opposing forces which contribute to differential growth: cytoskeleton contraction at the organoid core, and nuclear expansion during cell-cycle at the organoid perimeter. The wrinkling wavelength exhibits linear scaling with tissue thickness, consistent with polymer physics. Remarkably, lissencephalic (smooth brain) organoids exhibited reduced convulsions, linear scaling with an increased prefactor, and reduced elastic modulus. Our results support a physical mechanism for lissencephaly, in which change in tissue elasticity results in reduced folding.
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