Ccdc57 regulates cilia and left-right patterning in Xenopus.

During embryogenesis, the establishment of left-right (LR) asymmetry depends on directional fluid flow generated by motile cilia within the left-right organizer (LRO). Disruption of this process can lead to laterality disorders such as situs inversus, heterotaxy, and congenital heart defects. Here, we identify CCDC57 as a regulator of ciliary function and LR patterning. Depletion of ccdc57 via morpholino oligonucleotides (MOs) led to abnormal cilia in the multiciliated cells of the embryonic epidermis of Xenopus. Additionally, LR markers, dand5 and pitx2c were misexpressed resulting in defects in normal rightward cardiac looping. Finally, we identified a patient with situs inversus carrying compound heterozygous CCDC57 missense variants. We tested these variants in Xenopus depleted of ccdc57. Wild-type human CCDC57 mRNA, but not the patient variants, rescued ciliary structure and function. These findings establish ccdc57 as a regulator of LR patterning and suggest its potential involvement in human laterality disorders.