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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985904%3A_____%2F23%3A00580417" target="_blank" >RIV/67985904:_____/23:00580417 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14310/23:00132103 RIV/00216305:26620/23:PU149216

Výsledek na webu

<a href="https://www.life-science-alliance.org/content/6/12/e202302073" target="_blank" >https://www.life-science-alliance.org/content/6/12/e202302073</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.26508/lsa.202302073" target="_blank" >10.26508/lsa.202302073</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10605 - Developmental biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Life Science Alliance

ISSN

2575-1077

e-ISSN

2575-1077

Svazek periodika

6

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

16

Strana od-do

e202302073

Kód UT WoS článku

001094328500017

EID výsledku v databázi Scopus

2-s2.0-85175586751