Self-organizing optic-cup morphogenesis in three-dimensional culture
Abstract
Balanced organogenesis requires the orchestration of multiple cellular interactions to create the collective cell behaviours that progressively shape developing tissues. It is currently unclear how individual, localized parts are able to coordinate with each other to develop a whole organ shape. Here we report the dynamic, autonomous formation of the optic cup (retinal primordium) structure from a three-dimensional culture of mouse embryonic stem cell aggregates. Embryonic-stem-cell-derived retinal epithelium spontaneously formed hemispherical epithelial vesicles that became patterned along their proximal-distal axis. Whereas the proximal portion differentiated into mechanically rigid pigment epithelium, the flexible distal portion progressively folded inward to form a shape reminiscent of the embryonic optic cup, exhibited interkinetic nuclear migration and generated stratified neural retinal tissue, as seen in vivo. We demonstrate that optic-cup morphogenesis in this simple cell culture depends on an intrinsic self-organizing program involving stepwise and domain-specific regulation of local epithelial properties.
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Rx:GFP ESC maintenance, induced retinal neuroectoderm differentiation, and plasmid electroporation were performed as described previously (Eiraku et al., 2011; Li et al. 2020b, 2021).
“Rx:GFP ESC maintenance, induced retinal neuroectoderm differentiation, and plasmid electroporation were performed as described previously (Eiraku et al., 2011; Li et al. 2020b, 2021).”
From METTL3 uncouples chromatin accessibility from transcription during retinal development (2025) · cites this paper as Eiraku et al., 2011
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- Authors
- Eiraku, M., Takata, N., Ishibashi, H., Kawada, M., Sakakura, E., Okuda, S., Sekiguchi, K., Adachi, T., & Sasai, Y.
- Affiliations
- RIKEN (JP)
- Kyoto University (JP)
- Institute for Protein Research, The University of Osaka (JP)
- Corresponding author
- Eiraku, Mototsugu
- Sasai, Yoshiki
- ORCID
- Venue
- Nature
- Published
- 2011-04
- Volume
- 472
- Issue
- 7341
- Pages
- 51-56
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2074314696
- Cited by
- 2,001
- References
- 1
- Citations by year
- 2026: 76 · 2025: 116 · 2024: 129 · 2023: 146 · 2022: 159 · 2021: 181 · 2020: 160 · 2019: 143 · 2018: 148 · 2017: 148 · 2016: 133 · 2015: 117 · 2014: 118 · 2013: 95 · 2012: 89
- FWCI
- 44.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (22122006, 20001007, 21370104)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- optic cup morphogenesis, retinal development, embryonic stem cells, self-organization, 3D cell culture, retinal epithelium, pigment epithelium, neural retina, interkinetic nuclear migration, retinal repair, stem cell therapy, collective cell behavior
- MeSH terms
- Animals, Morphogenesis, Organ Culture Techniques, Retina, Cell Culture Techniques, Organogenesis, Regenerative Medicine, Mice, Embryonic Stem Cells, Neural Plate, Retinal Pigment Epithelium, Neural Stem Cells
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