Gdf11 regulates left-right asymmetry development through TGF-β signal

During the embryonic developmental stage in vertebrates, internal organs are arranged along the left–right axis. Disruptions in this process can result in congenital diseases or laterality disorders. The molecular mechanisms of left–right asymmetry in vertebrate development remain largely unclear. Due to its straightforward structure, zebrafish has become a favoured model for studying early laterality events. Here, we demonstrate that growth and development factor 11 (Gdf11) is essential for left–right development via TGF-β signalling. Morphological analysis showed that gdf11 morphants and mutants displayed clear heart and liver laterality disorders in a Nodal signal-dependent manner. Additionally, we found that Kupffer's vesicle formation and ciliogenesis were impaired following gdf11 deletion. We also observed that Gdf11 may form a heterodimer with Spaw, which promotes Smad2/3 phosphorylation and activates TGF-β signalling. Subsequently, Gdf11 promotes left–right laterality by stimulating Foxj1a and its target gene expression. In summary, we reveal a critical role of Gdf11 in left–right patterning, providing fundamental insights into the developmental process of left–right asymmetry.