Snail Transcriptionally Represses to Promote the Mesenchymal-Epithelial Transition in Ascidian Notochord Cells.

Mesenchymal-epithelial transition (MET) is a widely spread and evolutionarily conserved process across species during development. In embryogenesis, the notochord cells undergo the transition from the non-polarized mesenchymal state into the polarized endothelial-like state to initiate the lumen formation between adjacent cells. Based on previously screened MET-related transcription factors by ATAC-seq and Smart-Seq of notochord cells, () was selected for its high-level expression during this period. Our current knockout results demonstrated that was required for notochord cell MET. Importantly, overexpression of the transcription factor Brachyury in notochord cells resulted in a similar phenotype with failure of lumen formation and MET. More interestingly, expression of in the notochord cells at the late tailbud stage could partially rescue the MET defect caused by Brachyury-overexpression. These results indicated an inverse relationship between and during notochord cell MET, which was verified by RT-qPCR analysis. Moreover, the overexpression of could significantly inhibit the transcription of , and the CUT&Tag-qPCR analysis demonstrated that is directly bound to the upstream region of . In summary, we revealed that promoted the notochord cell MET and was essential for lumen formation via transcriptionally repressing .