Human brain organoids assemble functionally integrated bilateral optic vesicles

bioRxiv (Cold Spring Harbor Laboratory)

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.

Authors 20

1. Elke Gabriel

   Düsseldorf University Hospital · Heinrich Heine University Düsseldorf

   Affiliation as printed

   Institute of Human Genetics, University Hospital Düsseldorf, Heinrich-Heine-Universität, Universitätsstr. 1, 40225 Düsseldorf, Germany

   Institute of Human Genetics, University Hospital Düsseldorf, Heinrich-Heine-Universität, Universitätsstr. , 40225 Düsseldorf, Germany

2. Walid Albanna Aachen Department of Neurosurgery

   University of Cologne · RWTH Aachen University

   Affiliation as printed

   Department of Neurosurgery, RWTH Aachen University, Pauwelsstr. 30, 52074 Aachen, Germany

   Institute for Neurophysiology, University of Cologne, Robert-Koch Str. 39, 50931 Cologne, Germany

   Department of Neurosurgery, RWTH Aachen University, Pauwelsstr. 0, 52074 Aachen, Germany

3. Giovanni Pasquini

   University of Bonn · Center for Regenerative Therapies Dresden · Center for Molecular and Cellular Bioengineering · Technische Universität Dresden

   Affiliation as printed

   Department of Ophthalmology, Medical Faculty, University of Bonn, Bonn, Germany

   Technische Universität Dresden, Center for Molecular and Cellular Bioengineering (CMCB), Center for Regenerative Therapies Dresden (CRTD), Dresden, Germany

4. Anand Ramani

   Düsseldorf University Hospital · Heinrich Heine University Düsseldorf

   Affiliation as printed

   Institute of Human Genetics, University Hospital Düsseldorf, Heinrich-Heine-Universität, Universitätsstr. 1, 40225 Düsseldorf, Germany

   Institute of Human Genetics, University Hospital Düsseldorf, Heinrich-Heine-Universität, Universitätsstr. , 40225 Düsseldorf, Germany

5. Natasia Josipovic

   Universitätsmedizin Göttingen · University of Göttingen

   Affiliation as printed

   Institute of Pathology, University Medicine Göttingen, Georg-August University Göttingen, Robert-Koch-Straße 40, 37075 Göttingen, Germany

6. Aruljothi Mariappan

   Düsseldorf University Hospital · Heinrich Heine University Düsseldorf

   Affiliation as printed

   Institute of Human Genetics, University Hospital Düsseldorf, Heinrich-Heine-Universität, Universitätsstr. 1, 40225 Düsseldorf, Germany

   Institute of Human Genetics, University Hospital Düsseldorf, Heinrich-Heine-Universität, Universitätsstr. , 40225 Düsseldorf, Germany

7. Friedrich Schinzel

   Düsseldorf University Hospital · Heinrich Heine University Düsseldorf

   Affiliation as printed

   Institute of Human Genetics, University Hospital Düsseldorf, Heinrich-Heine-Universität, Universitätsstr. 1, 40225 Düsseldorf, Germany

   Institute of Human Genetics, University Hospital Düsseldorf, Heinrich-Heine-Universität, Universitätsstr. , 40225 Düsseldorf, Germany

8. Celeste M M. Karch

   Washington University in St. Louis

   Affiliation as printed

   Department of Psychiatry, Washington University in St Louis, St Louis MO 63116

9. Guobin Bao

   Universitätsmedizin Göttingen · University of Göttingen

   Affiliation as printed

   Institute of Neurophysiology and Cellular Biophysics, University Medicine Göttingen, Georg-August-Universität Göttingen, Humboldtallee 23, 37073 Göttingen, Germany

10. Marco Gottardo

    Düsseldorf University Hospital · Heinrich Heine University Düsseldorf

    Affiliation as printed

    Institute of Human Genetics, University Hospital Düsseldorf, Heinrich-Heine-Universität, Universitätsstr. 1, 40225 Düsseldorf, Germany

    Institute of Human Genetics, University Hospital Düsseldorf, Heinrich-Heine-Universität, Universitätsstr. , 40225 Düsseldorf, Germany

11. Jürgen Hescheler

    University of Cologne

    Affiliation as printed

    Institute for Neurophysiology, University of Cologne, Robert-Koch Str. 39, 50931 Cologne, Germany

12. Veronica Persico

    University of Siena

    Affiliation as printed

    Department of Life Sciences University of Siena, Via Aldo Moro 2, Siena 53100, Italy

    Department of Medical Biotechnologies, University of Siena, Via Aldo Moro 2, Siena 53100, Italy

    Department of Medical Biotechnologies, University of Siena, Via Aldo Moro 2, Siena 530, Italy

13. Silvio O. Rizzoli

    Universitätsmedizin Göttingen · University of Göttingen

    Affiliation as printed

    Institute of Neurophysiology and Cellular Biophysics, University Medicine Göttingen, Georg-August-Universität Göttingen, Humboldtallee 23, 37073 Göttingen, Germany

14. Janine Altmüller

    University of Cologne

    Affiliation as printed

    Cologne Center for Genomics (CCG), Universität zu Köln, Köln

15. Giuliano Callaini

    University of Siena · University of Cologne

    Affiliation as printed

    Cologne Center for Genomics (CCG), Universität zu Köln, Köln

    Department of Medical Biotechnologies, University of Siena, Via Aldo Moro 2, Siena 53100, Italy

    Department of Medical Biotechnologies, University of Siena, Via Aldo Moro 2, Siena 530, Italy

16. Argyris Papantonis

    Universitätsmedizin Göttingen · University of Göttingen

    Affiliation as printed

    Institute of Pathology, University Medicine Göttingen, Georg-August University Göttingen, Robert-Koch-Straße 40, 37075 Göttingen, Germany

17. Olivier Goureau

    Centre National de la Recherche Scientifique · Institut de la Vision · Inserm · Sorbonne Université

    Affiliation as printed

    Institut de la Vision, Sorbonne Université, INSERM, CNRS, F-75012 Paris, France

    Institut de la Vision, Sorbonne Université, INSERM, CNRS, F-750 Paris, France

18. Volker Busskamp

    University of Bonn · Center for Regenerative Therapies Dresden · Center for Molecular and Cellular Bioengineering · Technische Universität Dresden

    Affiliation as printed

    Department of Ophthalmology, Medical Faculty, University of Bonn, Bonn, Germany

    Technische Universität Dresden, Center for Molecular and Cellular Bioengineering (CMCB), Center for Regenerative Therapies Dresden (CRTD), Dresden, Germany

19. Toni Schneider

    University of Cologne

    Affiliation as printed

    Institute for Neurophysiology, University of Cologne, Robert-Koch Str. 39, 50931 Cologne, Germany

20. Jay Gopalakrishnan corresponding

    Düsseldorf University Hospital · Heinrich Heine University Düsseldorf

    Affiliation as printed

    Institute of Human Genetics, University Hospital Düsseldorf, Heinrich-Heine-Universität, Universitätsstr. 1, 40225 Düsseldorf, Germany

    Institute of Human Genetics, University Hospital Düsseldorf, Heinrich-Heine-Universität, Universitätsstr. , 40225 Düsseldorf, Germany