# Ccdc57 regulates cilia and left-right patterning in Xenopus

## TL;DR

This study shows that CCDC57 is important for cilia function and left-right body asymmetry in frogs and may be linked to human disorders like situs inversus.

## Contribution

The study identifies CCDC57 as a novel regulator of ciliary function and left-right patterning in Xenopus and links it to human laterality disorders.

## Key findings

- Depletion of ccdc57 in Xenopus leads to abnormal cilia and disrupted left-right patterning.
- Human CCDC57 variants from a patient with situs inversus fail to rescue ciliary defects in Xenopus.
- CCDC57 is essential for normal ciliary structure and function during embryonic development.

## Abstract

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.

Summary: CCDC57 is essential for motile cilia structure and left–right axis formation, linking Xenopus developmental defects to human laterality disorders.