DYX1C1 is required for axonemal dynein assembly and ciliary motility

Aarti Tarkar, Niki T. Loges, Christopher E. Slagle, Richard Francis, Gerard W. Dougherty, Joel V. Tamayo, Brett Shook, Marie Cantino, Daniel Schwartz, Charlotte Jahnke, Heike Olbrich, Claudius Werner, Johanna Raidt, Petra Pennekamp, Marouan Abouhamed, Rim Hjeij, Gabriele Köhler, Matthias Griese, You Li, Kristi LemkeNikolas Klena, Xiaoqin Liu, George Gabriel, Kimimasa Tobita, Martine Jaspers, Lucy C. Morgan, Adam J. Shapiro, Stef J.F. Letteboer, Dorus A. Mans, Johnny L. Carson, Margaret W. Leigh, Whitney E. Wolf, Serafine Chen, Jane S. Lucas, Alexandros Onoufriadis, Vincent Plagnol, Miriam Schmidts, Karsten Boldt, Ronald Roepman, Maimoona A. Zariwala, Cecilia W. Lo, Hannah M. Mitchison, Michael R. Knowles, Rebecca D. Burdine, Joseph J. Loturco, Heymut Omran

Research output: Contribution to journalArticlepeer-review

208 Scopus citations


DYX1C1 has been associated with dyslexia and neuronal migration in the developing neocortex. Unexpectedly, we found that deleting exons 2-4 of Dyx1c1 in mice caused a phenotype resembling primary ciliary dyskinesia (PCD), a disorder characterized by chronic airway disease, laterality defects and male infertility. This phenotype was confirmed independently in mice with a Dyx1c1 c.T2A start-codon mutation recovered from an N-ethyl-N-nitrosourea (ENU) mutagenesis screen. Morpholinos targeting dyx1c1 in zebrafish also caused laterality and ciliary motility defects. In humans, we identified recessive loss-of-function DYX1C1 mutations in 12 individuals with PCD. Ultrastructural and immunofluorescence analyses of DYX1C1-mutant motile cilia in mice and humans showed disruptions of outer and inner dynein arms (ODAs and IDAs, respectively). DYX1C1 localizes to the cytoplasm of respiratory epithelial cells, its interactome is enriched for molecular chaperones, and it interacts with the cytoplasmic ODA and IDA assembly factor DNAAF2 (KTU). Thus, we propose that DYX1C1 is a newly identified dynein axonemal assembly factor (DNAAF4).

Original languageEnglish (US)
Pages (from-to)995-1003
Number of pages9
JournalNature Genetics
Issue number9
StatePublished - Sep 2013

All Science Journal Classification (ASJC) codes

  • Genetics


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