Title:
Self-organized formation of 3D neural tissues in vitro

Mototsugu Eiraku
RIKEN, Center for Developmental Biology
4-Dimentional Tissue Analysis Unit

Abstract:
The balanced generation of organ requires the orchestration of multiple cellular interactions to create the collective cell behaviors that progressively shape developing tissues. In vitro generation of compound tissues with complex structures is a major challenge in cell biology. We report the dynamic, autonomous formation of the optic cup (retinal primordium) structure from a three-dimensional culture of mouse and human embryonic stem cell (ESC) aggregates. ESC-derived retinal epithelium spontaneously formed hemispherical epithelial vesicles that become patterned along its proximal-distal axis. While the rigid proximal portion differentiated into pigment epithelium, the flexible distal portion progressively folded inward to form a shape reminiscent of the embryonic optic cup. In long-term culture, the ESC-derived optic cup generates a fully stratified retinal tissue consisting of all major neural retina components. We demonstrate that optic-cup morphogenesis in this simple cell culture depends on an intrinsic self-organizing program involving stepwise and domain-specific regulations in local epithelial properties.

References:
Self-organizing optic-cup morphogenesis in three-dimensional culture.
Eiraku M et al., Nature, 472, 51-56 (2011)

Self-formation of layered neural structures in three-dimensional culture of ES cells.
Eiraku M et al., Curr Opin Neurobiol, 22,768-777 (2012)

Self-formation of optic cups and storable stratified neural retina from human ESCs.
Nakano et al., Cell Stem Cell, 12,771-785 (2012)