title: IFT56 regulates vertebrate developmental patterning by maintaining IFTB complex integrity and ciliary microtubule architecture.
abstract: Cilia are key regulators of animal development and depend on intraflagellar transport (IFT) proteins for their formation and function, yet the roles of individual IFT proteins remain unclear. We examined theIft56hopmouse mutant and reveal novel insight into the function of IFT56, a poorly understood IFTB protein.Ift56hopmice have normal cilia distribution but display defective cilia structure, including abnormal positioning and number of ciliary microtubule doublets. We show thatIft56hopcilia are unable to accumulate Gli proteins efficiently, resulting in developmental patterning defects in Shh signaling-dependent tissues such as the limb and neural tube. Strikingly, core IFTB proteins are unable to accumulate normally withinIft56hopcilia, including IFT88, IFT81 and IFT27, which are crucial for key processes such as tubulin transport and Shh signaling. IFT56 is required specifically for the IFTB complex, as IFTA components and proteins that rely on IFTA function are unaffected inIft56hopcilia. These studies define a distinct and novel role for IFT56 in IFTB complex integrity that is crucial for cilia structure and function and, ultimately, animal development.
authors.affiliation: Department of Genetics, Yale University, New Haven, CT 06520, USA.
authors.forename: Daisy
authors.initials: D
authors.lastname: Xin
authors.affiliation: Department of Genetics, Yale University, New Haven, CT 06520, USA.
authors.forename: Kasey J
authors.initials: KJ
authors.lastname: Christopher
authors.affiliation: Department of Genetics, Yale University, New Haven, CT 06520, USA.
authors.forename: Lewie
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.|W.M. Keck Foundation Biotechnology Resource Laboratory, Yale University, New Haven, CT 06520, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Kong
authors.affiliation: Department of Genetics, Yale University, New Haven, CT 06520, USA scott.weatherbee@yale.edu.
authors.forename: Scott D
authors.identifier: 0000-0002-0915-1329
authors.initials: SD
authors.lastname: Weatherbee
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D054468:Axoneme / Q000378:metabolism / Q000648:ultrastructure; D019521:Body Patterning; D002923:Cilia / Q000378:metabolism* / Q000648:ultrastructure; D018389:Codon, Nonsense / Q000235:genetics; D053823:Hedgehog Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D054259:Neural Tube / Q000378:metabolism; D010641:Phenotype; D017689:Polydactyly / Q000473:pathology; D015398:Signal Transduction; D014714:Vertebrates / Q000196:embryology* / Q000378:metabolism*; D000071676:Zinc Finger Protein GLI1 / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018389:Codon, Nonsense; D053823:Hedgehog Proteins; D000071676:Zinc Finger Protein GLI1
keywords: Cilia; Hedgehog signaling; IFT56; IFTB; Intraflagellar transport; Microtubule structure; TTC26