The primary cilium: a signalling centre during vertebrate development

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...

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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
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Abstract	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.
AbstractList	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. The primary cilium has recently stepped into the spotlight, as a flood of data demonstrate 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 (Hh) signal transduction. Formation of cilia, in turn, is regulated by other signaling pathways, possibly including the planar cell polarity pathway. The cilium therefore represents a nexus for signaling pathways during development. The connections between cilia and developmental signaling have begun to clarify the basis of human diseases associated with ciliary dysfunction. 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.
Audience	Academic
Author	Goetz, Sarah C Anderson, Kathryn V
AuthorAffiliation	Developmental Biology Program Sloan-Kettering Institute 1275 York Ave. New York, NY 10065
AuthorAffiliation_xml	– name: Developmental Biology Program Sloan-Kettering Institute 1275 York Ave. New York, NY 10065
Author_xml	– sequence: 1 givenname: Kathryn V surname: Anderson fullname: Anderson, Kathryn V organization: Developmental Biology Program, Sloan-Kettering Institute – sequence: 2 givenname: Sarah C surname: Goetz fullname: Goetz, Sarah C organization: Developmental Biology Program, Sloan-Kettering Institute
BackLink	http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22680782$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/20395968$$D View this record in MEDLINE/PubMed
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Snippet	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... 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... The primary cilium has recently stepped into the spotlight, as a flood of data demonstrate that this organelle has crucial roles in vertebrate development and...
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SubjectTerms	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
Title	The primary cilium: a signalling centre during vertebrate development
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