The primary cilium: a signalling centre during vertebrate development

• Published in: Nature reviews. Genetics Vol. 11; no. 5; pp. 331 - 344
• Main Authors: Anderson, Kathryn V, Goetz, Sarah C
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-05-2010; Nature Publishing Group
• Subjects: 631/136/2086; 631/208/2489/144; 631/80/128/1383; 631/80/86; Agriculture; Animal Genetics and Genomics; Animals; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cellular signal transduction; Cilia - metabolism; Cilia and ciliary motion; Embryos; Fundamental and applied biological sciences. Psychology; Gene Function; Genetic aspects; Genetic disorders; Genetics of eukaryotes. Biological and molecular evolution; Hedgehog Proteins - metabolism; Human Genetics; Humans; Kidneys; Kinesin; Mutation; Physiological aspects; Proteins; review-article; Risk factors; Signal Transduction; Transcription factors; Vertebrates; Vertebrates - embryology; United States; New York; United States > US; Development; Primary cilium; Vertebrata; Review
• ISSN: 1471-0056; 1471-0064
• DOI: 10.1038/nrg2774

Key Points
Over the past 10 years, primary cilia have been found to be required for hedgehog (Hh) signalling during development and have been implicated in cystic kidney disease and complex inherited disorders called ciliopathies.
In early vertebrate embryos, the primary cilium seems to be dedicated to transduction of Hh signals. Proteins required for building cilia, including the anterograde kinesin-2 motor, components of the intraflagellar transport B (IFTB) complex and a subset of basal-body-associated proteins, are required for Hh signalling in mice and zebrafish, and core components of the Hh pathway localize to cilia in a ligand-dependent manner. By contrast, the evidence suggests that other developmental signalling pathways do not depend on cilia.
All Hh signalling in embryos, adult stem cells and tumours depends on the primary cilium.
Based on the phenotypes of mutants that lack different components of the IFT machinery, regulated trafficking within the cilium determines the level of Hh signalling.
The fused (FU) and KIF7 proteins provide links between IFT and cilia and the Hh pathway. FU and COS2 (the homologue of KIF7) are required for Hh signalling in
Drosophila melanogaster
, whereas in other invertebrates they are required for ciliogenesis. In vertebrates, FU and KIF7 function in both cilia formation and Hh signalling.
Planar cell polarity (PCP) pathways can control the position of primary cilia, and mammalian homologues of proteins that function as PCP effectors in
D. melanogaster
are required for ciliogenesis. These connections between PCP and cilia position may have a role in cilia function in the inner ear and in the kidney.
A view is emerging of the primary cilium as a nexus for developmental signalling pathways. Cilia seem to be specialized for hedgehog signal transduction, and their formation is regulated by other signalling pathways. These findings have implications for human diseases that involve cilia dysfunction.
The primary cilium has recently stepped into the spotlight, as a flood of data show that this organelle has crucial roles in vertebrate development and human genetic diseases. Cilia are required for the response to developmental signals, and evidence is accumulating that the primary cilium is specialized for hedgehog signal transduction. The formation of cilia, in turn, is regulated by other signalling pathways, possibly including the planar cell polarity pathway. The cilium therefore represents a nexus for signalling pathways during development. The connections between cilia and developmental signalling have begun to clarify the basis of human diseases associated with ciliary dysfunction.