イシイ ヤスオ   Ishii Yasuo
  石井 泰雄
   所属   医学部 医学科
   職種   講師
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 Intrinsic lens potential of neural retina inhibited by Notch signaling as the cause of lens transdifferentiation.
掲載誌名 正式名:Developmental biology
略  称:Dev Biol
ISSNコード:(1095-564X)0012-1606(Linking)
掲載区分国外
巻・号・頁 421(2),pp.118-125
著者・共著者 Iida Hideaki, Ishii Yasuo, Kondoh Hisato
担当区分 2nd著者
発行年月 2017/01
概要 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, Prox1 and Pitx3, 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.
DOI 10.1016/j.ydbio.2016.11.004
PMID 27845051