石井 泰雄
   Department   Center for Medical and Nursing Education, Center for Medical and Nursing Education
   Position   Assistant Professor
Article types Original article
Language English
Peer review Peer reviewed
Title Intrinsic lens potential of neural retina inhibited by Notch signaling as the cause of lens transdifferentiation.
Journal Formal name:Developmental biology
Abbreviation:Dev Biol
ISSN code:(1095-564X)0012-1606(Linking)
Domestic / ForeginForegin
Volume, Issue, Page 421(2),pp.118-125
Author and coauthor Iida Hideaki, Ishii Yasuo, Kondoh Hisato
Authorship 2nd author
Publication date 2017/01
Summary 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