Nuclear Factor of Activated T Cells-5 Regulates Notochord Lumenogenesis in Chordate Larval Development

Osmoregulation is essential for organisms to adapt to the exterior environment and plays an important role in embryonic organogenesis. Tubular organ formation usually involves a hyperosmotic lumen environment. The mechanisms of how the cells respond and regulate lumen formation remain largely unknown. Here, we reported that the nuclear factor of activated T cells-5 ( ), the only transcription factor in the family involved in the cellular responses to hypertonic stress, regulated notochord lumen formation in chordate . ( - ) was expressed in notochord, and its expression level increased during notochord lumen formation and expansion. Knockout and expression of the dominant negative of in embryos resulted in the failure of notochord lumen expansion. We further demonstrated that the -NFAT5 transferred from the cytoplasm into nuclei in HeLa cells under the hyperosmotic medium, indicating can respond the hypertonicity. To reveal the underly mechanisms, we predicted potential downstream genes of and further validated interacted genes by the luciferase assay. The results showed that NFAT5 promoted expression. Furthermore, expression of a transport inactivity mutant of (L421P) in notochord led to the failure of lumen expansion, phenocopying that of knockout. These results suggest that - regulates notochord lumen expansion via the SLC26A6 axis. Taken together, our results reveal that the chordate responds to hypertonic stress and regulates lumen osmotic pressure via an ion channel pathway on luminal organ formation.