Transcriptional autoregulation of zebrafish tbx6 is required for somite segmentation

The presumptive somite boundary in the presomitic mesoderm (PSM) is defined by the anterior border of the expression domain of Tbx6 protein. During somite segmentation, the expression domain of Tbx6 is regressed by Ripply-meditated degradation of Tbx6 protein. Although the expression of zebrafish remains restricted to the PSM, the transcriptional regulation of remains poorly understood. Here, we show that the expression of zebrafish is maintained by transcriptional autoregulation. We find that a proximal-located -regulatory module, TR1, which contains two putative T-box sites, is required for somite segmentation in the intermediate body and for proper expression of segmentation genes. Embryos with deletion of TR1 exhibit significant reduction of expression at the 12-somite stage, although its expression is initially observed. Additionally, Tbx6 is associated with TR1 and activates its own expression in the anterior PSM. Furthermore, the anterior expansion of expression in mutants is suppressed in a TR1-dependent manner. The results suggest that the autoregulatory loop of zebrafish facilitates immediate removal of Tbx6 protein through termination of its own transcription at the anterior PSM.