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

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Authors

DUBAIC Marija PEŠKOVÁ Lucie HAMPL Marek WEISSOVÁ Kamila ÇELIKER Canan SHYLO Natalia A. HRUBA Eva KAVKOVA Michaela ZIKMUND Tomas WEATHERBEE Scott D KAISER Jozef BÁRTA Tomáš BUCHTOVÁ Marcela

Year of publication 2023
Type Article in Periodical
Magazine / Source Life Science Alliance
MU Faculty or unit

Faculty of Science

Citation
Web https://doi.org/10.26508/lsa.202302073
Doi http://dx.doi.org/10.26508/lsa.202302073
Keywords eye development; primary cilia; organoids; transmembrane protein
Description 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.
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