Self-organizing optic-cup morphogenesis in three-dimensional culture

Mototsugu Eiraku (), Nozomu Takata, Hiroki Ishibashi, Masako Kawada, Eriko Sakakura, Satoru Okuda, Kiyotoshi Sekiguchi, Taiji Adachi and Yoshiki Sasai ()
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Mototsugu Eiraku: Organogenesis and Neurogenesis Group, RIKEN Center for Developmental Biology
Nozomu Takata: Organogenesis and Neurogenesis Group, RIKEN Center for Developmental Biology
Hiroki Ishibashi: Institute for Frontier Medical Sciences, Kyoto University
Masako Kawada: Organogenesis and Neurogenesis Group, RIKEN Center for Developmental Biology
Eriko Sakakura: Organogenesis and Neurogenesis Group, RIKEN Center for Developmental Biology
Satoru Okuda: Institute for Frontier Medical Sciences, Kyoto University
Kiyotoshi Sekiguchi: Laboratory of Extracellular Matrix Biochemistry, Institute for Protein Research, Osaka University
Taiji Adachi: Institute for Frontier Medical Sciences, Kyoto University
Yoshiki Sasai: Organogenesis and Neurogenesis Group, RIKEN Center for Developmental Biology

Nature, 2011, vol. 472, issue 7341, 51-56

Abstract: 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.

Date: 2011
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DOI: 10.1038/nature09941

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