| First Author | Kinzel D | Year | 2010 |
| Journal | Dev Cell | Volume | 19 |
| Issue | 1 | Pages | 66-77 |
| PubMed ID | 20643351 | Mgi Jnum | J:162627 |
| Mgi Id | MGI:4819432 | Doi | 10.1016/j.devcel.2010.06.005 |
| Citation | Kinzel D, et al. (2010) Pitchfork regulates primary cilia disassembly and left-right asymmetry. Dev Cell 19(1):66-77 |
| abstractText | 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: |
