puc-header

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

43 Pages Posted: 12 Jul 2019 Publication Status: Review Complete

See all articles by Ji Pang

Ji Pang

Stowers Institute for Medical Research

Liang Le

Stowers Institute for Medical Research

Yi Zhou

Stowers Institute for Medical Research

Qiang Hou

Stowers Institute for Medical Research

Marina Thexton

Stowers Institute for Medical Research

Brandy Lewis

Stowers Institute for Medical Research

Timothy Corbin

Stowers Institute for Medical Research

Michael Durnin

Stowers Institute for Medical Research

Xin Gao

Stowers Institute for Medical Research

Hua Li

Stowers Institute for Medical Research

Allison Scott

Stowers Institute for Medical Research

Perera Anoja

Stowers Institute for Medical Research

Ruth Ashery-Padan

Tel Aviv University - Department of Human Molecular Genetics and Biochemistry

Deyue Yan

Shanghai Jiao Tong University (SJTU) - State Key Laboratory of Metal Matrix Composites

Ting Xie

Stowers Institute for Medical Research

More...

Abstract

Anterior segment dysgenesis is often associated with cornea diseases, cataracts and glaucoma. The ciliary body (CB) is a part of the anterior segment that secretes aqueous and vitreous humor that nourishes the eye. Although defective Notch signaling in the CB disrupts CB morphogenesis and causes eye degeneration, the underlying mechanisms remain missing. Here, this study shows that NOTCH signaling controls CB morphogenesis by directly regulating Nectin1 expression, and maintains the vitreous and eye structures by regulating the expression of vitreous proteins and gap junction protein Cx43. Genetic inactivation of Rbpj or both Notch2 and Notch3 in the CB not only disrupts CB morphogenesis but also causes CB epithelial detachment and vitreous shrinkage in the developing eye, and eye degeneration in adults. Molecularly, NOTCH signaling transcriptionally controls the expression of adhesion protein Nectin1 known to be essential for CB morphogenesis, and controls eye pressure and the vitreous through stabilizing gap junction protein Cx43 known to be important for CB secretion. Mechanistically, Nectin1 directly binds and stabilizes Cx43. Finally, NOTCH signaling in the CB also directly controls the expression of vitreous proteins. Therefore, this study has provided important mechanistic insight into how NOTCH signaling controls CB morphogenesis and secretion, and also further suggests the potential involvement of CB secretion in various eye diseases, including retinal degeneration.

Keywords: ciliary body, Notch signaling, Nectin, secretion, eye degeneration, vitreous, morphogenesis, adhesion

Suggested Citation

Pang, Ji and Le, Liang and Zhou, Yi and Hou, Qiang and Thexton, Marina and Lewis, Brandy and Corbin, Timothy and Durnin, Michael and Gao, Xin and Li, Hua and Scott, Allison and Anoja, Perera and Ashery-Padan, Ruth and Yan, Deyue and Xie, Ting, Notch Signaling Controls Ciliary Body Morphogenesis and Secretion by Directly Regulating Nectin Protein Expression (July 11, 2019). Available at SSRN: https://ssrn.com/abstract=3418423 or http://dx.doi.org/10.2139/ssrn.3418423
This version of the paper has not been formally peer reviewed.

Ji Pang

Stowers Institute for Medical Research

1000 E 50th Street
Kansas City, MO 64110
United States

Liang Le

Stowers Institute for Medical Research

1000 E 50th Street
Kansas City, MO 64110
United States

Yi Zhou

Stowers Institute for Medical Research

1000 E 50th Street
Kansas City, MO 64110
United States

Qiang Hou

Stowers Institute for Medical Research

1000 E 50th Street
Kansas City, MO 64110
United States

Marina Thexton

Stowers Institute for Medical Research

1000 E 50th Street
Kansas City, MO 64110
United States

Brandy Lewis

Stowers Institute for Medical Research

1000 E 50th Street
Kansas City, MO 64110
United States

Timothy Corbin

Stowers Institute for Medical Research

1000 E 50th Street
Kansas City, MO 64110
United States

Michael Durnin

Stowers Institute for Medical Research

1000 E 50th Street
Kansas City, MO 64110
United States

Xin Gao

Stowers Institute for Medical Research

1000 E 50th Street
Kansas City, MO 64110
United States

Hua Li

Stowers Institute for Medical Research

1000 E 50th Street
Kansas City, MO 64110
United States

Allison Scott

Stowers Institute for Medical Research

1000 E 50th Street
Kansas City, MO 64110
United States

Perera Anoja

Stowers Institute for Medical Research

1000 E 50th Street
Kansas City, MO 64110
United States

Ruth Ashery-Padan

Tel Aviv University - Department of Human Molecular Genetics and Biochemistry

Tel Aviv, 69978
Israel

Deyue Yan

Shanghai Jiao Tong University (SJTU) - State Key Laboratory of Metal Matrix Composites

Shanghai 200030, Shanghai 200052
China

Ting Xie (Contact Author)

Stowers Institute for Medical Research ( email )

1000 E 50th Street
Kansas City, MO 64110
United States

Click here to go to Cell.com

Paper statistics

Downloads
31
Abstract Views
560
PlumX Metrics