Pitchfork Regulates Primary Cilia Disassembly and Left-Right Asymmetry

Doris Kinzel, Karsten Boldt, Erica Ellen Davis, Ingo Burtscher, Dietrich Trümbach, Bill Diplas, Tania Attié-Bitach, Wolfgang Wurst, Elias Nicholas Katsanis, Marius Ueffing, Heiko Lickert*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

97 Scopus citations

Abstract

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:

Original languageEnglish (US)
Pages (from-to)66-77
Number of pages12
JournalDevelopmental Cell
Volume19
Issue number1
DOIs
StatePublished - Jul 2010

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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