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Primary Cilia in the Developing and Mature Brain
Open accessAbstract
Primary cilia were the largely neglected nonmotile counterparts of their better-known cousin, the motile cilia. For years these nonmotile cilia were considered evolutionary remnants of little consequence to cellular function. Fast forward 10 years and we now recognize primary cilia as key integrators of extracellular ligand-based signaling and cellular polarity, which regulate neuronal cell fate, migration, differentiation, as well as a host of adult behaviors. Important future questions will focus on structure-function relationships, their roles in signaling and disease and as areas of target for treatments.
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“Treatment of mouse hippocampal neurons with the SSTR3 ligand, somatostatin, stimulates recruitment of endogenous β-arrestin into SSTR3-positive cilia, leading to a rapid β-arrestin-2-dependent decrease in the ciliary SSTR3 167”
From Cellular signalling by primary cilia in development, organ function and disease (2019) · cites this paper as [167]
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“ciliary localization of SSTR3 is not affected in β-arrestin-2-deficient hippocampal neurons167.”
From Cellular signalling by primary cilia in development, organ function and disease (2019) · cites this paper as [167]
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“Neuronal cilia are enriched for certain GPCRs and downstream effector proteins 152, 166, 167”
From Cellular signalling by primary cilia in development, organ function and disease (2019) · cites this paper as [167]
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“Numerous studies have suggested the importance of the primary cilium in neuronal cells (Guemez-Gamboa et al. 2014).”
From Astrocyte-specific inhibition of the primary cilium suppresses C3 expression in reactive astrocyte (2024) · cites this paper as Guemez-Gamboa et al. 2014
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BackgroundmTOR in Acquired and Genetic Models of Epilepsy
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Investigating the Role of the Zinc Finger Protein ZC2HC1C on Autism Spectrum Disorder Susceptibility
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“…by the dendritic spine and signaling of primary cilium via ciliary AC3 signaling in both the MOE and CNS (Green et al., 2018; Guadiana et al., 2013; Guemez-Gamboa et al., 2014; Guo et al., 2019; Hildebrandt et al., 2011; Lee et al., 2020; Parisi, 2019; Reiter and Leroux, 2017; Sarkisian and…”
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“…0.01 vs control was speculated that the reduction of Inpp5e expression was an important factor in the occurrence of NTDs. Primary cilia play a pivotal role in early brain development, by regulating a variety of important intracellular signaling pathways, such as Wnt and hedgehog signaling [31, 32].”
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GFAP Polarity and Primary Cilia in Astrocytes of Mouse Brain
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Casanova, M., & Holliday, T. W. (2025) · BioEssays · doi:10.1002/bies.70100
Additional file 2 of The features of polyglutamine regions depend on their evolutionary stability
Mier, P., & Andrade-Navarro, M. A. (2020) · Figshare · doi:10.6084/m9.figshare.12364868
Riyahi, S., Liebermann-Lilie, N. D., Jacobs, A., Korsten, P., Mayer, U., & Schmoll, T. (2023) · Research Square · doi:10.21203/rs.3.rs-3456692/v1
TTBK2‐Driven Ciliogenesis Is Required for Intrinsic Neuronal Regeneration After Spinal Cord Injury
Zhang, R., Su, P., Tian, Z., Du, H., Wang, J., Yang, X., & Qi, Z. (2026) · CNS Neuroscience & Therapeutics · doi:10.1002/cns.70763
“During cortical development, PCs act as “sensing antennas” for pathways such as SHH and Wnt cascades, integrating external morphogenic signals to precisely regulate the fates of neural stem cells [13, 47, 48].”
Xie, Y., Zhang, T., Ouyang, A., Guan, M., Lin, X., Wang, L., Diao, X., Li, Y., He, W., Dong, Q., et al. (2026) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2026.106579
Study of Exon Junction Complex in mouse neural stem cells
Mishra, R. (2016) · theses.fr (ABES) · doi:10.70675/763ca66az53efz4562zb337z755d833bb64d
Reilly, M. L. (2018) · theses.fr (ABES) · doi:10.70675/dc69ccc1zaa2fz4147z8d1bzf306462e1009
Génétique et physiopathologie du syndrome de Lowe, analyse des aspects neurologiques
Héritier, A. (2019) · theses.fr (ABES) · doi:10.70675/de6a261fz5927z43bdza3cez77bae3ad1666
Rôle du cil primaire dans la migration des neuroblastes du courant de migration rostrale
Chaulet, M. (2019) · theses.fr (ABES) · doi:10.70675/d4a2bfe9z868az4e92z90c8zf24c941f943a
“Les revues résumant l'importance du cil dans le neurodéveloppement considère de ce fait que le cil primaire est essentiel à la migration (Guemez-Gamboa et al., 2014; Lepanto et al., 2016; Veland et al., 2014).”
Álvarez, G. O. (2020) · theses.fr (ABES) · doi:10.70675/c245dc66z5428z4d00z9ce9z00ea191284cb
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Hwang, D.-J., & Cho, J. (2026) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00091.2026
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Communication in the Depressed Brain
Sunzeri, F. (2026) · Springer eBooks · doi:10.1007/978-3-032-14465-2_7
Neuron-intrinsic and glial pathways regulate sensory cilia regeneration in adult C. elegansPreprint
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Primary cilia and neural computation
Teoh, A., Arinjay, M., Giri, D., & Phua, S. C. (2026) · Journal of Biomedical Science · doi:10.1186/s12929-026-01264-9
“A primary obstacle is disentangling developmental phenotypes from acute computational deficits, as germline perturbations of ciliary genes often produce widespread structural and circuit-level alterations during early brain development [30, 296].”
Námešná, A., Pickford, J., Hall, J., van den Bree, M. B. M., Tait, L., Wilkinson, L. S., & Jones, M. W. (2026) · Genes · doi:10.3390/genes17060716
“Although initially considered vestigial in mature neurons, it is now clear that primary cilia persist in postmitotic neurons and retain important cellular functions [203].”
The centrosome-cilium-centriolar satellite axis in neurodegenerative diseases
Şahin, U., & Firat‐Karalar, E. N. (2026) · EMBO Reports · doi:10.1038/s44319-026-00877-3
“They mediate key pathways such as Shh and Wnt during neurogenesis and also modulate stem cell activity, regeneration, and neuronal signaling in the adult nervous system (Guemez-Gamboa et al, 2014).”
Churkina, A. S., Shakhov, A. S., & Alieva, I. B. (2026) · Biochemistry (Moscow) · doi:10.1134/s0006297926601590
Primary Cilia of Astrocytes in the Retina in Development and Disease
Ning, K., Tran, M., Xia, X., Kowal, T. J., Wang, Q. K., Lo, C., Chen, S., Liu, Z., Li, T., Zhang, F., et al. (2026) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.67.11.7
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Noor, S., Kousar, N., & Bilal, S. (2026) · Chemical Product and Process Modeling · doi:10.1515/cppm-2026-0089
“Therefore, cilia are very essential for fl uid movement in various ciliated biological tissues [1 – 5].”
Primary cilia as a molecular convergence hub linking neurodevelopment and autism spectrum disorder
Boscato, A., Milesi, L., Biagioli, M., & Tata, A. (2026) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2026.1914796
DHA elongates the neuronal primary cilium through GPR40-mediated signaling
Karita, K., Yokota, M., Toyonaga, Y., Takase, R., Inagaki, N., Yamada, M. K., Yao, I., Toriyama, M., & Toriyama, M. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2026.1910684
Cd47 deficiency in mouse brain under excitotoxic stress
Kiamari, M., Perna, A., Santoro, M., Ariss, A. E., Berson, E., Zhao, J., Gajera, C. R., Fox, E. J., Montine, K. S., Aghaeepour, N., et al. (2026) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1014897
Metadata
- Authors
- Guemez-Gamboa, A., Coufal, N. G., & Gleeson, J. G.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Gleeson, Joseph G.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2014-05
- Volume
- 82
- Issue
- 3
- Pages
- 511-521
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC4104280
- OpenAlex
- W2074800621
- Cited by
- 296
- References
- 99
- Citations by year
- 2026: 22 · 2025: 29 · 2024: 21 · 2023: 26 · 2022: 27 · 2021: 22 · 2020: 28 · 2019: 34 · 2018: 17 · 2017: 21 · 2016: 23 · 2015: 22 · 2014: 4
- FWCI
- 3.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of California Institute for Mexico and the United States
- National Institute of Neurological Disorders and Stroke (R13NS053097, 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
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- primary cilia, brain development, neuronal polarity, extracellular signaling, neuronal cell fate, neuronal migration, neuronal differentiation
- MeSH terms
- Animals, Brain, Brain Diseases, Cell Movement, Cilia, Humans, Signal Transduction, Cell Polarity
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