Role of ciliopathy protein TMEM107 in eye development: insights from a mouse model and retinal organoid

0580417 - ÚŽFG 2024 RIV US eng J - Journal Article
Dubaic, Marija - Pešková, L. - Hampl, Marek - Weissová, Kamila - Celiker, C. - Shylo, N. - Hrubá, Eva - Kavková, M. - Zikmund, T. - Weatherbee, S. D. - Kaiser, J. - Bárta, Tomáš - Buchtová, Marcela
Role of ciliopathy protein TMEM107 in eye development: insights from a mouse model and retinal organoid.
Life Science Alliance. Roč. 6, č. 12 (2023), č. článku e202302073. E-ISSN 2575-1077
R&D Projects: GA ČR(CZ) GA21-05146S; GA MŠMT EF15_003/0000460; GA MŠMT(CZ) LM2023050; GA MZd NU22-07-00380
Institutional support: RVO:67985904
Keywords : primary cilis * TMEM107 * mouse model
OECD category: Developmental biology
Impact factor: 4.4, year: 2022
Method of publishing: Open access
https://www.life-science-alliance.org/content/6/12/e202302073

Primary cilia are cellular surface projections enriched in receptors and signaling molecules, acting as signaling hubs that respond to stimuli. Malfunctions in primary cilia have been linked to human diseases, including retinopathies and ocular defects. Here, we focus on TMEM107, a protein localized to the transition zone of primary cilia. TMEM107 mutations were found in patients with Joubert and Meckel-Gruber syndromes. A mouse model lacking Tmem107 exhibited eye defects such as anophthalmia and microphthalmia, affecting retina differentiation. Tmem107 expression during prenatal mouse development correlated with phenotype occurrence, with enhanced expression in differentiating retina and optic stalk. TMEM107 deficiency in retinal organoids resulted in the loss of primary cilia, down-regulation of retina-specific genes, and cyst formation. Knocking out TMEM107 in human ARPE-19 cells prevented primary cilia formation and impaired response to Smoothened agonist treatment because of ectopic activation of the SHH pathway. Our data suggest TMEM107 plays a crucial role in early vertebrate eye development and ciliogenesis in the differentiating retina.
Permanent Link: https://hdl.handle.net/11104/0349189