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  • Review Article
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Primary cilia in neurodevelopmental disorders

Key Points

  • Primary cilia are single hair-like, non-motile sensory organelles that are found on the surface of almost all cells in vertebrates

  • Physiological roles of primary cilia include chemical and mechanical sensation, signal transduction, and control of cell growth

  • Mutations in genes relating to the structure or function of primary cilia are responsible for a clinically and genetically heterogeneous class of disorders known as ciliopathies

  • A subset of ciliopathies are commonly associated with intellectual disability and brain malformations that can include midbrain and/or hindbrain malformations, agenesis of the corpus callosum, and encephalocoele

  • Primary cilia have key roles in mediating morphogenic and mitogenic signals during development, and perturbations in these pathways probably contribute to the neurological features of ciliopathies

Abstract

Primary cilia are generally solitary organelles that emanate from the surface of almost all vertebrate cell types. Until recently, details regarding the function of these structures were lacking; however, extensive evidence now suggests that primary cilia have critical roles in sensing the extracellular environment, and in coordinating developmental and homeostatic signalling pathways. Furthermore, disruption of these functions seems to underlie a diverse spectrum of disorders, known as primary ciliopathies. These disorders are characterized by wide-ranging clinical and genetic heterogeneity, but with substantial overlap among distinct conditions. Indeed, ciliopathies are associated with a large variety of manifestations that often include distinctive neurological findings. Herein, we review neurological features associated with primary ciliopathies, highlight genotype–phenotype correlations, and discuss potential mechanisms underlying these findings.

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Figure 1: Structure and organization of the primary cilium.
Figure 2: Typical clinical features in ciliopathies with CNS involvement.
Figure 3: Common MRI findings in ciliopathies with CNS involvement.

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Acknowledgements

The authors would like to thank Andrea Poretti, Lihadh Al-Gazali, Hulya Kayserili and Maha Zaki for supplying the descriptive MRI images and clinical pictures that have enriched this Review. E. M. Valente acknowledges research support from the European Research Council (ERC Starting Grant #260888), the Italian Ministry of Health (Ricerca Corrente 2013, Ricerca Finalizzata Malattie Rare 2008), and Telethon Foundation Italy (grant #GGP13146). J. G. Gleeson acknowledges research support from the Howard Hughes Medical Institute and research funding from the NIH (grants R01NS048453 and R01NS052455).

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E. M. Valente, E. Gibbs and J. G. Gleeson contributed substantially to all stages of the preparation of the manuscript. R. O. Rosti made a substantial contribution to discussion of the content, writing and review/editing of the manuscript before submission.

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Correspondence to Joseph G. Gleeson.

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Valente, E., Rosti, R., Gibbs, E. et al. Primary cilia in neurodevelopmental disorders. Nat Rev Neurol 10, 27–36 (2014). https://doi.org/10.1038/nrneurol.2013.247

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