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A Zebrafish Loss‐of‐Function Model for Human CFAP53 Mutations Reveals Its Specific Role in Laterality Organ Function
Author(s) -
Noël Emily S.,
Momenah Tarek S.,
AlDagriri Khalid,
AlSuwaid Abdulrahman,
AlShahrani Safar,
Jiang Hui,
Willekers Sven,
Oostveen Yara Y.,
Chocron Sonja,
Postma Alex V.,
Bhuiyan Zahurul A.,
Bakkers Jeroen
Publication year - 2016
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22928
Subject(s) - zebrafish , biology , laterality , function (biology) , loss function , mutation , genetics , neuroscience , computational biology , microbiology and biotechnology , gene , phenotype
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.