Self-organizing optic-cup morphogenesis in three-dimensional culture
Self-organizing optic-cup morphogenesis in three-dimensional culture
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DOI：
10.1038/nature09941
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发表时间：
2011-04-07
期刊：
影响因子：
64.8
通讯作者：
Sasai, Yoshiki
中科院分区：
文献类型：
--
作者：
Eiraku, Mototsugu;Takata, Nozomu;Sasai, Yoshiki
平衡的器官发生需要协调多个细胞的相互作用，以创造集体的细胞行为，逐步形成发育中的组织。目前尚不清楚单个局部部分如何能够相互协调以形成整个器官形状。在这里，我们报告的动态，自主形成的视杯（视网膜原基）结构的三维培养的小鼠胚胎干细胞聚集。胚胎干细胞衍生的视网膜上皮自发形成半球形上皮囊泡，其沿其近端-远端轴沿着形成图案。而近端部分分化成机械刚性色素上皮，灵活的远端部分逐渐向内折叠，形成一个形状，让人想起胚胎视杯，表现出interkinetic核迁移和生成分层的神经视网膜组织，在体内看到的。我们表明，在这个简单的细胞培养的视杯形态取决于一个内在的自组织程序，涉及逐步和域特定的调节局部上皮特性。
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.