Human brain organoids assemble functionally integrated bilateral optic vesicles


  • E. Gabriel
  • W. Albanna
  • Gi. Pasquini
  • A. Ramani
  • N. Josipovic
  • A. Mariappan
  • F. Schinzel
  • C.M. Karch
  • G. Bao
  • M. Gottardo
  • A.A. Suren
  • J. Hescheler
  • K. Nagel-Wolfrum
  • V. Persico
  • S.O. Rizzoli
  • J. Altmüller
  • M.G. Riparbelli
  • G. Callaini
  • O. Goureau
  • A. Papantonis
  • V. Busskamp
  • T. Schneider
  • J. Gopalakrishnan


  • Cell Stem Cell


  • Cell Stem Cell 28 (10): 1740-1757.e8


  • During embryogenesis, optic vesicles develop from the diencephalon via a multistep process of organogenesis. Using induced pluripotent stem cell (iPSC)-derived human brain organoids, we attempted to simplify the complexities and demonstrate formation of forebrain-associated bilateral optic vesicles, cellular diversity, and functionality. Around day 30, brain organoids attempt to assemble optic vesicles, which develop progressively as visible structures within 60 days. These optic vesicle-containing brain organoids (OVB-organoids) constitute a developing optic vesicle's cellular components, including primitive corneal epithelial and lens-like cells, retinal pigment epithelia, retinal progenitor cells, axon-like projections, and electrically active neuronal networks. OVB-organoids also display synapsin-1, CTIP-positive myelinated cortical neurons, and microglia. Interestingly, various light intensities could trigger photosensitive activity of OVB-organoids, and light sensitivities could be reset after transient photobleaching. Thus, brain organoids have the intrinsic ability to self-organize forebrain-associated primitive sensory structures in a topographically restricted manner and can allow interorgan interaction studies within a single organoid.