Pitchfork regulates primary cilia disassembly and left-right asymmetry.


Journal Article

A variety of developmental disorders have been associated with ciliary defects, yet the controls that govern cilia disassembly are largely unknown. Here we report a mouse embryonic node gene, which we named Pitchfork (Pifo). Pifo associates with ciliary targeting complexes and accumulates at the basal body during cilia disassembly. Haploinsufficiency causes a unique node cilia duplication phenotype, left-right asymmetry defects, and heart failure. This phenotype is likely relevant in humans, because we identified a heterozygous R80K PIFO mutation in a fetus with situs inversus and cystic liver and kidneys, and in patient with double-outflow right ventricle. We show that PIFO, but not R80K PIFO, is sufficient to activate Aurora A, a protooncogenic kinase that induces cilia retraction, and that Pifo/PIFO mutation causes cilia retraction, basal body liberation, and overreplication defects. Thus, the observation of a disassembly phenotype in vivo provides an entry point to understand and categorize ciliary disease. AUTHOR AUDIO:

Full Text

Cited Authors

  • Kinzel, D; Boldt, K; Davis, EE; Burtscher, I; Trümbach, D; Diplas, B; Attié-Bitach, T; Wurst, W; Katsanis, N; Ueffing, M; Lickert, H

Published Date

  • July 20, 2010

Published In

Volume / Issue

  • 19 / 1

Start / End Page

  • 66 - 77

PubMed ID

  • 20643351

Pubmed Central ID

  • 20643351

Electronic International Standard Serial Number (EISSN)

  • 1878-1551

Digital Object Identifier (DOI)

  • 10.1016/j.devcel.2010.06.005


  • eng

Conference Location

  • United States