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Cellular signalling by primary cilia in development, organ function and disease

Nature Reviews Nephrology (2019) | Download Citation


Primary cilia project in a single copy from the surface of most vertebrate cell types; they detect and transmit extracellular cues to regulate diverse cellular processes during development and to maintain tissue homeostasis. The sensory capacity of primary cilia relies on the coordinated trafficking and temporal localization of specific receptors and associated signal transduction modules in the cilium. The canonical Hedgehog (HH) pathway, for example, is a bona fide ciliary signalling system that regulates cell fate and self-renewal in development and tissue homeostasis. Specific receptors and associated signal transduction proteins can also localize to primary cilia in a cell type-dependent manner; available evidence suggests that the ciliary constellation of these proteins can temporally change to allow the cell to adapt to specific developmental and homeostatic cues. Consistent with important roles for primary cilia in signalling, mutations that lead to their dysfunction underlie a pleiotropic group of diseases and syndromic disorders termed ciliopathies, which affect many different tissues and organs of the body. In this Review, we highlight central mechanisms by which primary cilia coordinate HH, G protein-coupled receptor, WNT, receptor tyrosine kinase and transforming growth factor-β (TGFβ)/bone morphogenetic protein (BMP) signalling and illustrate how defects in the balanced output of ciliary signalling events are coupled to developmental disorders and disease progression.

Key points

  • Primary cilia emanate in a single copy from the centrosomal mother centriole (basal body) at the surface of most vertebrate cell types.

  • Primary cilia possess a unique lipid and receptor composition and detect and convey extracellular cues to control cellular processes during development and in tissue homeostasis.

  • Current evidence suggests that primary cilia coordinate a variety of signalling pathways, including those regulated by Hedgehog (HH), G protein-coupled receptors (GPCRs), WNT, receptor tyrosine kinases (RTKs) and transforming growth factor-β (TGFβ)/bone morphogenetic protein (BMP), to control developmental processes, tissue plasticity and organ function.

  • The ability of primary cilia to balance the output of cellular signalling is dynamic and relies on the differentiation state and microenvironment of the cell.

  • Dysfunction of primary cilia underlies a pleiotropic group of diseases and syndromic disorders termed ciliopathies, affecting many different organs in the body.

  • Mechanistic insight into ciliary coordination of spatiotemporal signalling networks is critical for understanding the aetiology of ciliopathies and for the discovery of novel ciliopathy disease genes and drug targets.

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The authors’ work presented in this Review was supported by Independent Research Fund Denmark (6108-00457B and 8020-00162B to S.T.C. and L.B.P.), the Danish Cancer Society (R146-A9590-16-S2 to L.B.P. and Z.A.), Brødrene Hartmanns Fond (A31662 to L.B.P.), research project grant R21 MH107021 from the US National Institutes of Health (NIH) National Institute of Mental Health (to K.M.), a grant from Alex’s Lemonade Foundation (to S.M.), a Welch Foundation Grant (I-1906 to S.M.) and an R01 grant from NIH (1R01GM113023 to S.M.). The authors are grateful to S. K. Morthorst, University of Copenhagen, for help with formatting the references and the three reviewers for their insightful and constructive comments. The authors apologize to those authors whose work has not been cited because of space limitations.

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Nature Reviews Nephrology thanks M. Nachury, P. Tran and other anonymous reviewer(s) for their contribution to the peer review of this work.

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  1. Department of Biology, Section of Cell Biology and Physiology, University of Copenhagen, Copenhagen, Denmark

    • Zeinab Anvarian
    • , Lotte Bang Pedersen
    •  & Søren Tvorup Christensen
  2. Department of Biological Chemistry and Pharmacology, The Ohio State University, Columbus, OH, USA

    • Kirk Mykytyn
  3. Department of Cell Biology, UT Southwestern Medical Center, Dallas, TX, USA

    • Saikat Mukhopadhyay


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All authors researched the data for this article, discussed its content, wrote and reviewed the paper and edited the manuscript before submission.

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Correspondence to Søren Tvorup Christensen.

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