NOTCH Signaling Controls Ciliary Body Morphogenesis and Secretion by Directly Regulating Nectin Protein Expression.
Cx43
IOP
NOTCH signaling
Nectin1
anterior segment
aqueous humor
ciliary body
eye degeneration
morphogenesis
secretion
viteous
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
12 01 2021
12 01 2021
Historique:
received:
19
07
2020
revised:
20
11
2020
accepted:
14
12
2020
entrez:
13
1
2021
pubmed:
14
1
2021
medline:
5
1
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33440163
pii: S2211-1247(20)31592-8
doi: 10.1016/j.celrep.2020.108603
pmc: PMC8422303
mid: NIHMS1732309
pii:
doi:
Substances chimiques
NOTCH2 protein, human
0
NOTCH3 protein, human
0
Nectins
0
Notch2 protein, mouse
0
Notch3 protein, mouse
0
Receptor, Notch2
0
Receptor, Notch3
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
108603Subventions
Organisme : NEI NIH HHS
ID : R01 EY027441
Pays : United States
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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