ZFIN ID: ZDB-PUB-151105-3
A zebrafish Loss-of-Function Model for Human CFAP53 Mutations Reveals its Specific Role in Laterality Organ Function
Noël, E.S., Momenah, T.S., Al-Dagriri, K., Al-Suwaid, A., Al-Shahrani, S., Jiang, H., Willekers, S., Oostveen, Y.Y., Chocron, S., Postma, A.V., Bhuiyan, Z.A., Bakkers, J.
Date: 2016
Source: Human Mutation   37(2): 194-200 (Journal)
Registered Authors: Bakkers, Jeroen, Chocron, Sonja, Noël, Emily
Keywords: CCDC11, CFAP53, Heterotaxy, cilia, congenital heart defect, laterality, zebrafish
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
PubMed: 26531781 Full text @ Hum. Mutat.
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 3 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 randomisation 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. This article is protected by copyright. All rights reserved.