NOTCH Signaling Controls Ciliary Body Morphogenesis and Secretion by Directly Regulating Nectin Protein Expression

Autor: Ji Pang, Liang Le, Yi Zhou, Renjun Tu, Qiang Hou, Dai Tsuchiya, Nancy Thomas, Yongfu Wang, Zulin Yu, Richard Alexander, Marina Thexton, Brandy Lewis, Timothy Corbin, Michael Durnin, Hua Li, Ruth Ashery-Padan, Deyue Yan, Ting Xie
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Cell Reports, Vol 34, Iss 2, Pp 108603- (2021)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2020.108603
Popis: Summary: Anterior segment dysgenesis is often associated with cornea diseases, cataracts, and glaucoma. In the anterior segment, the ciliary body (CB) containing inner and outer ciliary epithelia (ICE and OCE) secretes aqueous humor that maintains intraocular pressure (IOP). However, CB development and function remain poorly understood. Here, this study shows that NOTCH signaling in the CB maintains the vitreous, IOP, and eye structures by regulating CB morphogenesis, aqueous humor secretion, and vitreous protein expression. Notch2 and Notch3 function via RBPJ in the CB to control ICE-OCE adhesion, CB morphogenesis, aqueous humor secretion, and protein expression, thus maintaining IOP and eye structures. Mechanistically, NOTCH signaling transcriptionally controls Nectin1 expression in the OCE to promote cell adhesion for driving CB morphogenesis and to directly stabilize Cx43 for controlling aqueous humor secretion. Finally, NOTCH signaling directly controls vitreous protein secretion in the ICE. Therefore, this study provides important insight into CB functions and involvement in eye diseases.
Databáze: Directory of Open Access Journals