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Cilia in the nervous system: linking cilia function and neurodevelopmental disorders
Open accessAbstract
PURPOSE OF REVIEW: Ciliopathies are genetic disorders caused by defects of primary ciliary structure and/or function and are characterized by pleiotropic clinical features. The ciliopathies include several partially overlapping syndromes such as Joubert syndrome, Bardet-Biedl syndrome and Meckel-Gruber syndrome, all of which have pronounced neurodevelopmental features. Here we focus on potential roles of cilia in central nervous system function, to explore how impairments may cause brain malformation and neurodevelopmental disease. RECENT FINDINGS: Cilia have long been considered as 'sensory cellular antennae', responding as chemo-sensors, mechano-sensors and thermo-sensors, although their roles in development were not well understood until recently. The surprising finding that disparate syndromes are all due to defects of the primary cilia, along with the recent advances in genetics, has helped elucidate further roles of primary cilia beyond sensory functions. Several molecules that are associated with key signaling pathways have been discovered in primary cilia. These include sonic hedgehog, wingless, planar cell polarity and fibroblast growth factor, which are essential for many cellular processes. Additionally, mutations in 'ciliome' genes have largely shown developmental defects such as abnormal body axis and brain malformation, implying disrupted cilia-related signaling pathways. Accordingly, the emerging theme is that primary cilia may play roles as modulators of signal transduction to help shape cellular responses within the environmental context during both development and homeostasis. SUMMARY: The link between cilia and signal pathways has become a framework for understanding the pathogenesis of ciliopathies. Despite recent progress in ciliary biology, fundamental questions remain about how cilia regulate neuronal function in the central nervous system. Therefore, investigation of ciliary function in the nervous system may reveal cilia-modulating mechanisms in neurodevelopmental processes, as well as suggest new treatments for disease.
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“All ciliopathies share one phenotype, cognitive impairment [37–42].”
From Amyloid-β interrupts canonical Sonic hedgehog signaling by distorting primary cilia structure (2018) · cites this paper as [41]
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“Impaired Shh signaling results in similar phenotypes as those observed in patients with disrupted cilia structure or function [37–42].”
From Amyloid-β interrupts canonical Sonic hedgehog signaling by distorting primary cilia structure (2018) · cites this paper as [41]
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“Indeed several of the monogenic causes of ASD, including TSC [56] and Joubert Syndrome [57, 58] show manifestations of abnormal axon path finding or migration abnormalities that are known to lead to alterations in brain structural connectivity.”
From Genetics of autism spectrum disorders (2011) · cites this paper as [58]
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Metadata
- Authors
- Lee, J. E., & Gleeson, J. G.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Gleeson, Joseph G
- Venue
- Current Opinion in Neurology
- Published
- 2011-04
- Volume
- 24
- Issue
- 2
- Pages
- 98-105
- ISSN
- 1350-7540 (ISSN-L)
- PMC
- PMC3984876
- OpenAlex
- W2018911042
- Cited by
- 185
- References
- 65
- Citations by year
- 2026: 10 · 2025: 11 · 2024: 9 · 2023: 10 · 2022: 13 · 2021: 12 · 2020: 11 · 2019: 16 · 2018: 9 · 2017: 6 · 2016: 9 · 2015: 13 · 2014: 16 · 2013: 15 · 2012: 19
- FWCI
- 1.90
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Current Opinion in Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of Neurological Disorders and Stroke (R01NS048453, R01NS052455)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Fetal and Pediatric Neurological Disorders
- Keywords
- primary cilia, ciliopathies, neurodevelopmental disorders, Joubert syndrome, Bardet-Biedl syndrome, Meckel-Gruber syndrome, brain malformations, Sonic hedgehog signaling, planar cell polarity signaling, FGF signaling, Wingless signaling, signal transduction, central nervous system development
- MeSH terms
- Abnormalities, Multiple, Central Nervous System, Cerebellar Diseases, Cerebellum, Developmental Disabilities, Cilia, Eye Abnormalities, Humans, Nervous System Diseases, Neurons, Retina, Syndrome, Signal Transduction, Kidney Diseases, Cystic
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