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

Organogenesis and Neurogenesis Group, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
Nature (Impact Factor: 41.46). 04/2011; 472(7341):51-6. DOI: 10.1038/nature09941
Source: PubMed


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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Available from: Taiji Adachi, Sep 08, 2014
    • "The resultant structures exhibit an incredible level of organ-specific architectural detail. In the realm of brain organogenesis, an early example of this selforganizing property was the growth of an optic cup structure that possessed retinal morphology (Eiraku et al., 2011). A subsequent study created cerebral organoids that formed several discrete brain regions, including the cerebral hemispheres, hippocampus, ventricular system, and choroid plexus (Lancaster et al., 2013). "
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    • "Subsequently, the apical side of the NR gradually expands more than the basal side to complete invagination. Once the NR field is specified, NE cells start neurogenesis following a temporal pattern that mimics the in vivo situation, enabling the sequential generation of various retinal cell populations organized in a layer-like structure, which resembles the early neonatal eye of rodents (Eiraku et al., 2011; Nakano et al., 2012; Osakada et al., 2009) (Fig. 4B). Another aspect of the selforganizing property of retinal development from human PSCs was demonstrated more recently (Kuwahara et al., 2015), in which a specific stem cell niche called the retinal ciliary margin (RCM) (Agathocleous and Harris, 2009),which is located at the boundary of the NR and RPE, could be generated in vitro and displayed the potential to produce retinal progenitors, which in turn generate various retinal subtypes including photoreceptors (Fig. 4C). "
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    • "Organogenesis of ectodermal organs, such as teeth (Fig. S1 and Text S1 in the Supporting material), hair, and the optic cup, involves a large-scale deformation process that is critical for later development (Eiraku et al., 2011; Jernvall et al., 1994; Paus et al., 1999; Toyoshima et al., 2012; Vaahtokari et al., 1996). In the early stage of tooth development, a bud of dental epithelium grows into a cap structure with an invaginated tip (Fig. 1A, white arrowhead). "
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