The primary cilium: a signalling centre during vertebrate development
TLDR
The connections between cilia and developmental signalling have begun to clarify the basis of human diseases associated with ciliary dysfunction, and the cilium represents a nexus for signalling pathways during development.Abstract:
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.read more
Citations
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Journal ArticleDOI
The mechanisms of Hedgehog signalling and its roles in development and disease.
TL;DR: Novel biological insights are revealed into the function of HH lipidation in the secretion and transport of this ligand and details of the signal transduction pathway, which involves Patched 1, Smoothened and GLI proteins, as well as, in vertebrates, primary cilia.
Journal ArticleDOI
Post-translational regulation of the microtubule cytoskeleton: mechanisms and functions
TL;DR: Functional studies demonstrating that post-translational modifications may regulate microtubule functions through an amazing range of mechanisms are demonstrated.
Journal ArticleDOI
Gli Proteins in Development and Disease
Chi-chung Hui,Stephane Angers +1 more
TL;DR: The regulation of Gli proteins during development is described and possible mechanisms for their abnormal activation during tumorigenesis are discussed, including noncanonical mechanisms independent of Hedgehog signaling.
Journal ArticleDOI
A transition zone complex regulates mammalian ciliogenesis and ciliary membrane composition
Francesc R. Garcia-Gonzalo,Kevin C. Corbit,María Salomé Sirerol-Piquer,Gokul Ramaswami,Edgar A. Otto,Thomas R. Noriega,Allen D. Seol,Jon F. Robinson,Christopher L. Bennett,Dragana Josifova,José Manuel García-Verdugo,Nicholas Katsanis,Friedhelm Hildebrandt,Friedhelm Hildebrandt,Jeremy F. Reiter +14 more
TL;DR: A transition zone complex of Meckel and Joubert syndrome proteins regulates ciliary assembly and trafficking, suggesting that transition zone dysfunction is the cause of these ciliopathies.
Journal ArticleDOI
Mechanisms and functions of Hedgehog signalling across the metazoa
TL;DR: An updated overview of the mechanisms and functions of this signalling pathway is provided, highlighting the conserved and divergent features of the pathway, as well as some of the common themes in its deployment that have emerged from recent studies.
References
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Journal ArticleDOI
Randomization of Left–Right Asymmetry due to Loss of Nodal Cilia Generating Leftward Flow of Extraembryonic Fluid in Mice Lacking KIF3B Motor Protein
Shigenori Nonaka,Yosuke Tanaka,Yasushi Okada,Sen Takeda,Akihiro Harada,Yoshimitsu Kanai,Mizuho A. Kido,Nobutaka Hirokawa +7 more
TL;DR: The data suggest that KIF3B is essential for the left-right determination through intraciliary transportation of materials for ciliogenesis of motile primary cilia that could produce a gradient of putative morphogen along the left–right axis in the node.
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Vertebrate Smoothened functions at the primary cilium
Kevin C. Corbit,Pia Aanstad,Veena Singla,Andrew R. Norman,Didier Y.R. Stainier,Jeremy F. Reiter +5 more
TL;DR: It is shown that mammalian Smoothened (Smo), a seven-transmembrane protein essential for Hh signalling, is expressed on the primary cilium, and Hh-dependent translocation to cilia is essential for Smo activity, suggesting that Smo acts at thePrimary cilia.
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Patched1 Regulates Hedgehog Signaling at the Primary Cilium
TL;DR: The role of primary cilia in regulation of Patched1 (Ptc1), the receptor for Sonic Hedgehog (Shh), is investigated and it is found that Ptc1 localized to cilia and inhibited Smoothened (Smo) by preventing its accumulation within cilia.
Journal ArticleDOI
Hedgehog signalling in the mouse requires intraflagellar transport proteins
Danwei Huangfu,Aimin Liu,Aimin Liu,Andrew S. Rakeman,Andrew S. Rakeman,Noel S. Murcia,Lee Niswander,Lee Niswander,Kathryn V. Anderson +8 more
TL;DR: Genetic analysis shows that Wim, Polaris and the IFT motor protein Kif3a are required for Hedgehog signalling at a step downstream of Patched1 (the Hedgehog receptor) and upstream of direct targets of hedgehog signalling.
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A Core Complex of BBS Proteins Cooperates with the GTPase Rab8 to Promote Ciliary Membrane Biogenesis
Maxence V. Nachury,Alexander V. Loktev,Qihong Zhang,Christopher J. Westlake,Johan Peränen,Andreas Merdes,Diane C. Slusarski,Richard H. Scheller,J. Fernando Bazan,Val C. Sheffield,Peter K. Jackson +10 more
TL;DR: The data reveal that BBS may be caused by defects in vesicular transport to the cilium, and a complex composed of seven highly conserved BBS proteins is identified, the BBSome, which localizes to nonmembranous centriolar satellites in the cytoplasm but also to the membrane of the cILium.