Human brain organoids assemble functionally integrated bilateral optic vesicles

Gabriel, E.; Albanna, W.; Pasquini, G.; Ramani, A.; Josipovic, N.; Mariappan, A.; Schinzel, F.; Karch, C. M.; Bao, G.; Gottardo, M.; Hescheler, J.; Persico, V.; Rizzoli, S. O.; Altmüller, J.; Callaini, G.; Papantonis, A.; Goureau, O.; Busskamp, V.; Schneider, T.; Gopalakrishnan, J.

doi:10.1101/2021.03.30.437506

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bioRxiv · 10.1101/2021.03.30.437506

Human brain organoids assemble functionally integrated bilateral optic vesicles

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Abstract

During embryogenesis, optic vesicles develop from the diencephalon via a complex process of organogenesis. Using iPSC-derived human brain organoids, we attempted to simplify the complexities and demonstrate the formation of forebrain-associated bilateral optic vesicles, cellular diversity, and functionality. Around day thirty, brain organoids could assemble optic vesicles, which progressively develop as visible structures within sixty days. These optic vesicle-containing brain organoids (OVB-Organoids) constitute a developing optic vesicles cellular components, including the primitive cornea and lens-like cells, developing photoreceptors, retinal pigment epithelia, axon-like projections, and electrically active neuronal networks. Besides, OVB-Organoids also display synapsin-1, CTIP-positive, myelinated cortical neurons, and microglia. Interestingly, various light intensities could trigger photoreceptor activity of OVB-Organoids, and light sensitivities could be reset after a transient photo bleach blinding. Thus, brain organoids have the intrinsic ability to self-organize forebrain-associated primitive sensory structures in a topographically restricted manner and can allow conducting interorgan interaction studies within a single organoid.

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Gabriel, E., Albanna, W., Pasquini, G., Ramani, A., Josipovic, N., Mariappan, A., Schinzel, F., Karch, C. M., Bao, G., Gottardo, M., Hescheler, J., Persico, V., Rizzoli, S. O., Altmüller, J., Callaini, G., Papantonis, A., Goureau, O., Busskamp, V., Schneider, T., Gopalakrishnan, J.. 2021-03-30. Human brain organoids assemble functionally integrated bilateral optic vesicles. https://doi.org/10.1101/2021.03.30.437506

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