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

J 2023

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

DUBAIC, Marija; Lucie PEŠKOVÁ; Marek HAMPL; Kamila WEISSOVÁ; Canan ÇELIKER et. al.

Basic information

Original name

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

Authors

Edition

Life Science Alliance, Life Science Alliance LLC, 2023, 2575-1077

Other information

Language

English

Type of outcome

Article in a journal

Field of Study

10603 Genetics and heredity

Country of publisher

United States of America

Confidentiality degree

is not subject to a state or trade secret

References:

URL

Impact factor

Impact factor: 3.300

RIV identification code

RIV/00216224:14310/23:00132103

Organization unit

Faculty of Science

DOI

https://doi.org/10.26508/lsa.202302073

UT WoS

001094328500017

EID Scopus

2-s2.0-85175586751

Keywords in English

eye development; primary cilia; organoids; transmembrane protein

Abstract

In the original language

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.

Links

GA21-05146S, research and development project

Name: Úloha TMEM107 ve vývoji kraniofaciálních struktur

Investor: Czech Science Foundation

NU22-07-00380, research and development project

Name: Aplikace retinálních buněk a organoidů ve funkční diagnostice a léčbě ztráty zraku u Bardet-Biedlova syndromu

Investor: Ministry of Health of the CR, Subprogram 1 - standard

90250, large research infrastructures

Name: Czech-BioImaging III

Cite

DUBAIC, Marija; Lucie PEŠKOVÁ; Marek HAMPL; Kamila WEISSOVÁ; Canan ÇELIKER; Natalia A. SHYLO; Eva HRUBA; Michaela KAVKOVA; Tomas ZIKMUND; Scott D WEATHERBEE; Jozef KAISER; Tomáš BÁRTA and Marcela BUCHTOVÁ. Role of ciliopathy protein TMEM107 in eye development: insights from a mouse model and retinal organoid. Life Science Alliance. Life Science Alliance LLC, 2023, vol. 6, No 12, p. 1-16. ISSN 2575-1077. Available from: https://doi.org/10.26508/lsa.202302073.

@article{2333477,
   author = {Dubaic, Marija and Pešková, Lucie and Hampl, Marek and Weissová, Kamila and Çeliker, Canan and Shylo, Natalia A. and Hruba, Eva and Kavkova, Michaela and Zikmund, Tomas and Weatherbee, Scott D and Kaiser, Jozef and Bárta, Tomáš and Buchtová, Marcela},
   article_number = {12},
   doi = {https://doi.org/10.26508/lsa.202302073},
   keywords = {eye development; primary cilia; organoids; transmembrane protein},
   language = {eng},
   issn = {2575-1077},
   journal = {Life Science Alliance},
   title = {Role of ciliopathy protein TMEM107 in eye development: insights from a mouse model and retinal organoid},
   url = {https://doi.org/10.26508/lsa.202302073},
   volume = {6},
   year = {2023}
}

TY  - JOUR
ID  - 2333477
AU  - 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
PY  - 2023
TI  - Role of ciliopathy protein TMEM107 in eye development: insights from a mouse model and retinal organoid
JF  - Life Science Alliance
VL  - 6
IS  - 12
SP  - 1-16
EP  - 1-16
PB  - Life Science Alliance LLC
SN  - 25751077
KW  - eye development
KW  - primary cilia
KW  - organoids
KW  - transmembrane protein
UR  - https://doi.org/10.26508/lsa.202302073
N2  - 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.
ER  -

DUBAIC, Marija; Lucie PEŠKOVÁ; Marek HAMPL; Kamila WEISSOVÁ; Canan $\backslash$C CELIKER; Natalia A. SHYLO; Eva HRUBA; Michaela KAVKOVA; Tomas ZIKMUND; Scott D WEATHERBEE; Jozef KAISER; Tomáš BÁRTA and Marcela BUCHTOVÁ. Role of ciliopathy protein TMEM107 in eye development: insights from a mouse model and retinal organoid. \textit{Life Science Alliance}. Life Science Alliance LLC, 2023, vol.~6, No~12, p.~1-16. ISSN~2575-1077. Available from: https://doi.org/10.26508/lsa.202302073.

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