Regulatory mechanism of the periodic expression of Ripply3 during pharyngeal arch segmentation

咽弓是出现在脊椎动物胚胎前部的一种短暂的节段结构。在心脏、胸腺等正常器官发生的后期，需要适当的PA分割。我们最近发现Ripply3基因在发育中的PA中高度表达。有趣的是，突出的表达首先出现在未分割的PA区域，然后随着PA分割的进行而减少。因此，Ripply3的表达周期性地由前向后转移。为了阐明Ripply3在PA片段中独特表达的分子机制，我们构建了由Ripply3启动子驱动的EGFP报告基因转基因小鼠。EGFP表达重现了Ripply3的内源性表达模式。此外，该启动子在体外被Tbx1激活，而被Ripply3自身抑制。这些研究表明Tbx1和Ripply3对Ripply3的周期性表达具有重要作用。

Pharyngeal arch (PA) is a transient segmental structure appears in the anterior part of vertebrate embryos. Appropriate PA segmentation is required for the normal organogenesis such as heart, thymus, and others at later stages. We recently identified the Ripply3 gene that is highly expressed in the developing PA. Interestingly, the prominent expression emerges in the unsegmented PA region first, and then it decreases as PA segmentation proceeds. Thus, Ripply3 expression shifts periodically from anterior to posterior. To elucidate the molecular mechanism of the unique expression of Ripply3 during PA segmentation, we generated the EGFP reporter transgenic mouse driven by Ripply3 promoter. The EGFP expression recapitulated the endogenous expression pattern of Ripply3. Furthermore, the promoter is activated by Tbx1, and repressed by Ripply3 itself in vitro. These studies revealed that Tbx1 and Ripply3 have important roles for the periodic expression of Ripply3.