An Eye Organoid Approach Identifies Six3 Suppression of R-spondin 2 as a Critical Step in Mouse Neuroretina Differentiation.
An Eye Organoid Approach Identifies Six3 Suppression of R-spondin 2 as a Critical Step in Mouse Neuroretina Differentiation.
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DOI：
10.1016/j.celrep.2017.10.041
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发表时间：
2017-11-07
期刊：
影响因子：
8.8
通讯作者：
Oliver G
中科院分区：
文献类型：
--
作者：
Takata N;Abbey D;Fiore L;Acosta S;Feng R;Gil HJ;Lavado A;Geng X;Interiano A;Neale G;Eiraku M;Sasai Y;Oliver G
胚胎干细胞（ESC）和诱导多能干细胞（iPSC）的自组织三维组织培养的最新进展提供了一个体外模型，概括了体内发育步骤的许多方面。使用表达Rax-GFP的ESC、新产生的Six 3 −/− iPSC和条件性无效Six 3delta/f;Rax-Cre ESC，我们鉴定了Six 3对R-spondin 2（Rspo 2）的抑制是视泡形态发生和神经视网膜分化过程中的必需步骤。我们在体内验证了这些结果，表明转基因小鼠胚胎的前神经板中Rspo 2的瞬时异位表达足以抑制神经视网膜分化。此外，使用嵌合眼类器官测定，我们确定Six 3-null细胞在视泡形成和神经视网膜分化过程中发挥非细胞自主抑制作用。我们的研究结果进一步验证了类器官培养系统作为一种可靠和快速的替代方案，以确定和评估参与眼形态发生和神经视网膜分化的基因在体内。
Recent advances in self-organizing, 3-dimensional tissue cultures of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) provided an in vitro model that recapitulates many aspects of the in vivo developmental steps. Using Rax-GFP expressing ESCs, newly generated Six3−/− iPSCs and conditional null Six3delta/f;Rax-Cre ESCs we identified Six3 repression of R-spondin 2 (Rspo2) as a required step during optic vesicle morphogenesis and neuroretina differentiation. We validated these results in vivo by showing that transient ectopic expression of Rspo2 in the anterior neural plate of transgenic mouse embryos was sufficient to inhibit neuroretina differentiation. Additionally, using a chimeric eye organoid assay we determined that Six3-null cells exert a non-cell autonomous repressive effect during optic vesicle formation and neuroretina differentiation. Our results further validate the organoid culture system as a reliable and fast alternative to identify and evaluate genes involved in eye morphogenesis and neuroretina differentiation in vivo.
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影响因子：
10.5
作者：
de Lau W;Peng WC;Gros P;Clevers H
通讯作者：
Clevers H
影响因子：
5.9
作者：
Assawachananont, Juthaporn;Mandai, Michiko;Okamoto, Satoshi;Yamada, Chikako;Eiraku, Mototsugu;Yonemura, Shigenobu;Sasai, Yoshiki;Takahashi, Masayo
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Takahashi, Masayo
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作者：
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影响因子：
8.8
作者：
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通讯作者：
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作者：
Irizarry, RA;Hobbs, B;Speed, TP
通讯作者：
Speed, TP