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Human brain organoids assemble functionally integrated bilateral optic vesicles

Elke Gabriel, Walid Albanna, Giovanni Pasquini, Anand Ramani, Natasia Josipovic, Aruljothi Mariappan, Friedrich Schinzel, Celeste M. Karch, Guobin Bao, Marco Gottardo, Jürgen Hescheler, Veronica Persico, Silvio O. Rizzoli, Janine Altmüller, Giuliano Callaini, Argyris Papantonis, Olivier Goureau, Volker Busskamp, Toni Schneider, Jay Gopalakrishnan
doi: https://doi.org/10.1101/2021.03.30.437506
Elke Gabriel
1Institute of Human Genetics, University Hospital Düsseldorf, Heinrich-Heine-Universität, Universitätsstr. 1, 40225 Düsseldorf, Germany
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Walid Albanna
2Institute for Neurophysiology, University of Cologne, Robert-Koch Str. 39, 50931 Cologne, Germany
3Department of Neurosurgery, RWTH Aachen University, Pauwelsstr. 30, 52074 Aachen, Germany
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Giovanni Pasquini
4Technische Universität Dresden, Center for Molecular and Cellular Bioengineering (CMCB), Center for Regenerative Therapies Dresden (CRTD), Dresden, Germany
5Department of Ophthalmology, Medical Faculty, University of Bonn, Bonn, Germany
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Anand Ramani
1Institute of Human Genetics, University Hospital Düsseldorf, Heinrich-Heine-Universität, Universitätsstr. 1, 40225 Düsseldorf, Germany
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Natasia Josipovic
6Institute of Pathology, University Medicine Göttingen, Georg-August University Göttingen, Robert-Koch-Straße 40, 37075 Göttingen, Germany
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Aruljothi Mariappan
1Institute of Human Genetics, University Hospital Düsseldorf, Heinrich-Heine-Universität, Universitätsstr. 1, 40225 Düsseldorf, Germany
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Friedrich Schinzel
1Institute of Human Genetics, University Hospital Düsseldorf, Heinrich-Heine-Universität, Universitätsstr. 1, 40225 Düsseldorf, Germany
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Celeste M. Karch
7Department of Psychiatry, Washington University in St Louis, St Louis MO 63116
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Guobin Bao
8Institute of Neurophysiology and Cellular Biophysics, University Medicine Göttingen, Georg-August-Universität Göttingen, Humboldtallee 23, 37073 Göttingen, Germany
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Marco Gottardo
1Institute of Human Genetics, University Hospital Düsseldorf, Heinrich-Heine-Universität, Universitätsstr. 1, 40225 Düsseldorf, Germany
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Jürgen Hescheler
2Institute for Neurophysiology, University of Cologne, Robert-Koch Str. 39, 50931 Cologne, Germany
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Veronica Persico
9Department of Life Sciences University of Siena, Via Aldo Moro 2, Siena 53100, Italy
10Department of Medical Biotechnologies, University of Siena, Via Aldo Moro 2, Siena 53100, Italy
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Silvio O. Rizzoli
8Institute of Neurophysiology and Cellular Biophysics, University Medicine Göttingen, Georg-August-Universität Göttingen, Humboldtallee 23, 37073 Göttingen, Germany
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Janine Altmüller
11Cologne Center for Genomics (CCG), Universität zu Köln, Köln
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Giuliano Callaini
10Department of Medical Biotechnologies, University of Siena, Via Aldo Moro 2, Siena 53100, Italy
11Cologne Center for Genomics (CCG), Universität zu Köln, Köln
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Argyris Papantonis
6Institute of Pathology, University Medicine Göttingen, Georg-August University Göttingen, Robert-Koch-Straße 40, 37075 Göttingen, Germany
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Olivier Goureau
12Institut de la Vision, Sorbonne Université, INSERM, CNRS, F-75012 Paris, France
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Volker Busskamp
4Technische Universität Dresden, Center for Molecular and Cellular Bioengineering (CMCB), Center for Regenerative Therapies Dresden (CRTD), Dresden, Germany
5Department of Ophthalmology, Medical Faculty, University of Bonn, Bonn, Germany
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Toni Schneider
2Institute for Neurophysiology, University of Cologne, Robert-Koch Str. 39, 50931 Cologne, Germany
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Jay Gopalakrishnan
1Institute of Human Genetics, University Hospital Düsseldorf, Heinrich-Heine-Universität, Universitätsstr. 1, 40225 Düsseldorf, Germany
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  • For correspondence: jay.gopalakrishnan@hhu.de
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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 vesicle’s 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.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted March 30, 2021.
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Human brain organoids assemble functionally integrated bilateral optic vesicles
Elke Gabriel, Walid Albanna, Giovanni Pasquini, Anand Ramani, Natasia Josipovic, Aruljothi Mariappan, Friedrich Schinzel, Celeste M. Karch, Guobin Bao, Marco Gottardo, Jürgen Hescheler, Veronica Persico, Silvio O. Rizzoli, Janine Altmüller, Giuliano Callaini, Argyris Papantonis, Olivier Goureau, Volker Busskamp, Toni Schneider, Jay Gopalakrishnan
bioRxiv 2021.03.30.437506; doi: https://doi.org/10.1101/2021.03.30.437506
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Human brain organoids assemble functionally integrated bilateral optic vesicles
Elke Gabriel, Walid Albanna, Giovanni Pasquini, Anand Ramani, Natasia Josipovic, Aruljothi Mariappan, Friedrich Schinzel, Celeste M. Karch, Guobin Bao, Marco Gottardo, Jürgen Hescheler, Veronica Persico, Silvio O. Rizzoli, Janine Altmüller, Giuliano Callaini, Argyris Papantonis, Olivier Goureau, Volker Busskamp, Toni Schneider, Jay Gopalakrishnan
bioRxiv 2021.03.30.437506; doi: https://doi.org/10.1101/2021.03.30.437506

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