A Zebrafish Loss-of-Function Model for Human CFAP53 Mutations Reveals Its Specific Role in Laterality Organ Function

Hum Mutat. 2016 Feb;37(2):194-200. doi: 10.1002/humu.22928. Epub 2015 Dec 2.


Establishing correct left-right asymmetry during embryonic development is crucial for proper asymmetric positioning of the organs. Congenital heart defects, such as dextrocardia, transposition of the arteries, and inflow or outflow tract malformations, comprise some of the most common birth defects and may be attributed to incorrect establishment of body laterality. Here, we identify new patients with dextrocardia who have mutations in CFAP53, a coiled-coil domain containing protein. To elucidate the mechanism by which CFAP53 regulates embryonic asymmetry, we used genome editing to generate cfap53 zebrafish mutants. Zebrafish cfap53 mutants have specific defects in organ laterality and randomization of asymmetric gene expression. We show that cfap53 is required for cilia rotation specifically in Kupffer's vesicle, the zebrafish laterality organ, providing a mechanism by which patients with CFAP53 mutations develop dextrocardia and heterotaxy, and confirming previous evidence that left-right asymmetry in humans is regulated through cilia-driven fluid flow in a laterality organ.

Keywords: CCDC11; CFAP53; cilia; congenital heart defect; heterotaxy; laterality; zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Body Patterning / genetics
  • Cilia / metabolism
  • Cilia / pathology
  • Conserved Sequence
  • Cytoskeletal Proteins / genetics*
  • Cytoskeletal Proteins / metabolism
  • DNA Mutational Analysis
  • Dextrocardia / genetics*
  • Dextrocardia / metabolism
  • Dextrocardia / pathology
  • Embryo, Nonmammalian
  • Embryonic Development / genetics
  • Female
  • Gene Expression
  • Heterotaxy Syndrome / genetics*
  • Heterotaxy Syndrome / metabolism
  • Heterotaxy Syndrome / pathology
  • Humans
  • Lateral Line System / embryology
  • Lateral Line System / metabolism
  • Male
  • Molecular Sequence Data
  • Mutation*
  • Pedigree
  • Siblings
  • Zebrafish / embryology
  • Zebrafish / genetics*
  • Zebrafish / metabolism
  • Zebrafish Proteins / genetics*
  • Zebrafish Proteins / metabolism


  • CFAP53 protein, human
  • CFAP53 protein, zebrafish
  • Cytoskeletal Proteins
  • Zebrafish Proteins