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

被引：1458

作者：

Eiraku, Mototsugu ^{[1
,2
]}

Takata, Nozomu ^{[1
]}

Ishibashi, Hiroki ^{[3
]}

Kawada, Masako ^{[1
]}

Sakakura, Eriko ^{[1
,2
]}

Okuda, Satoru ^{[3
]}

Sekiguchi, Kiyotoshi ^{[4
]}

Adachi, Taiji ^{[3
,5
]}

Sasai, Yoshiki ^{[1
,2
]}

机构：

[1] RIKEN Ctr Dev Biol, Organogenesis & Neurogenesis Grp, Kobe, Hyogo 6500047, Japan

[2] RIKEN Ctr Dev Biol, Dimens Tissue Anal Unit 4, Kobe, Hyogo 6500047, Japan

[3] Kyoto Univ, Inst Frontier Med Sci, Dept Biomech, Kyoto 6068507, Japan

[4] Osaka Univ, Inst Prot Res, Lab Extracellular Matrix Biochem, Suita, Osaka 5650871, Japan

[5] RIKEN, VCAD Syst Res Program, Computat Cell Biomech Team, Wako, Saitama 3510198, Japan

来源：

NATURE | 2011年 / 472卷 / 7341期

关键词：

RETINAL-PIGMENT EPITHELIUM; EMBRYONIC STEM-CELLS; EYE DEVELOPMENT; APICAL CONSTRICTION; MOUSE EMBRYOS; NEURAL PLATE; SHAPE CHANGE; VESICLE; DIFFERENTIATION; RHO;

D O I：

10.1038/nature09941

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：51 / U73

页数：8

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