Intrinsic lens potential of neural retina inhibited by Notch signaling as the cause of lens transdifferentiation
Intrinsic lens potential of neural retina inhibited by Notch signaling as the cause of lens transdifferentiation
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Notch信号抑制神经视网膜的内在晶状体电位作为晶状体转分化的原因
DOI：
10.1016/j.ydbio.2016.11.004
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Kondoh Hisato
中科院分区：
文献类型：
--
作者：
Iida Hideaki;Ishii Yasuo;Kondoh Hisato
鸟类胚胎神经视网膜在扩散培养条件下产生晶状体。由于细胞类型的明显变化，这种现象被认为是转分化的范例。在这里，我们阐明了潜在的机制。视网膜到透镜的转分化发生在扩散培养中，这表明它是由改变的细胞-细胞相互作用触发的。因此，我们基于Notch信号在视网膜神经发生中的作用来测试Notch信号的参与。从E8视网膜开始，在对照扩散培养物中20天后，少量表达stac的透镜细胞开始发育。相比之下，在第2天后向培养物中添加Notch信号抑制剂强烈促进了从第11天开始的透镜发育，并且δ-晶状体蛋白表达水平增加了10倍。Notch信号抑制后，调节眼发育早期的转录因子基因Prox 1和Pitx 3依次被激活。这些观察结果表明，透镜分化潜力是内在的神经视网膜，这种潜力是由Notch信号在正常胚胎发生过程中抑制。因此，Notch抑制通过解除对透镜发育的神经视网膜内在程序的抑制而导致透镜转分化。
Embryonic neural retinas of avians produce lenses under spreading culture conditions. This phenomenon has been regarded as a paradigm of transdifferentiation due to the overt change in cell type. Here we elucidated the underlying mechanisms. Retina-to-lens transdifferentiation occurs in spreading cultures, suggesting that it is triggered by altered cell-cell interactions. Thus, we tested the involvement of Notch signaling based on its role in retinal neurogenesis. Starting from E8 retina, a small number of crystallin-expressing lens cells began to develop after 20 days in control spreading cultures. By contrast, addition of Notch signal inhibitors to cultures after day 2 strongly promoted lens development beginning at day 11, and a 10-fold increase in δ-crystallin expression level. After Notch signal inhibition, transcription factor genes that regulate the early stage of eye development,Prox1andPitx3, were sequentially activated. These observations indicate that the lens differentiation potential is intrinsic to the neural retina, and this potential is repressed by Notch signaling during normal embryogenesis. Therefore, Notch suppression leads to lens transdifferentiation by disinhibiting the neural retina-intrinsic program of lens development.