Loss of Ciliary Gene Bbs8 Results in Physiological Defects in the Retinal Pigment Epithelium
Open Access
- 18 February 2021
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Cell and Developmental Biology
Abstract
Primary cilia are sensory organelles vital for developmental and physiological processes. Their dysfunction causes a range of phenotypes including retinopathies. Although primary cilia have been described in the retinal pigment epithelium (RPE), little is known about their contribution to biological processes within this tissue. Ciliary proteins are increasingly being identified in non-ciliary locations and might carry out additional functions, disruption of which possibly contributes to pathology. The RPE is essential for maintaining photoreceptor cells and visual function. We demonstrate that upon loss of Bbs8, predominantly thought to be a ciliary gene, the RPE shows changes in gene and protein expression initially involved in signaling pathways and developmental processes, and at a later time point RPE homeostasis and function. Differentially regulated molecules affecting the cytoskeleton and cellular adhesion, led to defective cellular polarization and morphology associated with a possible epithelial-to-mesenchymal transition (EMT)-like phenotype. Our data highlights the benefit of combinatorial "omics" approaches with in vivo data for investigating the function of ciliopathy proteins. It also emphasizes the importance of ciliary proteins in the RPE and their contribution to visual disorders, which must be considered when designing treatment strategies for retinal degeneration.Funding Information
- Deutsche Forschungsgemeinschaft
- Alexander von Humboldt-Stiftung (Sofya Kovalevskaya Award)
- Johannes Gutenberg-Universität Mainz
This publication has 68 references indexed in Scilit:
- Fiji: an open-source platform for biological-image analysisNature Methods, 2012
- Microphthalmia-associated Transcription Factor (MITF) Promotes Differentiation of Human Retinal Pigment Epithelium (RPE) by Regulating microRNAs-204/211 ExpressionJournal of Biological Chemistry, 2012
- Ciliopathies: an expanding disease spectrumPediatric Nephrology, 2011
- Loss of Bardet–Biedl syndrome protein-8 (BBS8) perturbs olfactory function, protein localization, and axon targetingProceedings of the National Academy of Sciences of the United States of America, 2011
- Ciliogenesis: building the cell's antennaNature Reviews Molecular Cell Biology, 2011
- The primary cilium: a signalling centre during vertebrate developmentNature Reviews Genetics, 2010
- Systematic and integrative analysis of large gene lists using DAVID bioinformatics resourcesNature Protocols, 2008
- MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantificationNature Biotechnology, 2008
- When cilia go bad: cilia defects and ciliopathiesNature Reviews Molecular Cell Biology, 2007
- Essential role for MFG-E8 as ligand for αvβ5 integrin in diurnal retinal phagocytosisProceedings of the National Academy of Sciences of the United States of America, 2007