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首页> 外文期刊>Development >TBX2 and TBX3 act downstream of canonical WNT signaling in patterning and differentiation of the mouse ureteric mesenchyme
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TBX2 and TBX3 act downstream of canonical WNT signaling in patterning and differentiation of the mouse ureteric mesenchyme

机译：TBX2和TBX3在鼠标输尿管间充质模型的图案化和分化中的规范WNT信号传导下游

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摘要

The organized array of smooth muscle cells (SMCs) and fibroblasts in the walls of visceral tubular organs arises by patterning and differentiation of mesenchymal progenitors surrounding the epithelial lumen. Here, we show that the TBX2 and TBX3 transcription factors have novel and required roles in regulating these processes in the murine ureter. Co-expression of TBX2 and TBX3 in the inner mesenchymal region of the developing ureter requires canonical WNT signaling. Loss of TBX2/TBX3 in this region disrupts activity of two crucial drivers of the SMC program, Foxf1 and BMP4 signaling, resulting in decreased SMC differentiation and increased extracellular matrix. Transcriptional profiling and chromatin immunoprecipitation experiments revealed that TBX2/TBX3 directly repress expression of the WNT antagonists Dkk2 and Shisa2, the BMP antagonist Bmper and the chemokine Cxcl12. These findings suggest that TBX2/TBX3 are effectors of canonical WNT signaling in the ureteric mesenchyme that promote SMC differentiation by maintaining BMP4 and WNT signaling in the inner region, while restricting CXCL12 signaling to the outer layer of fibroblast-fated mesenchyme.
机译：通过图案化和分化上皮腔周围的间充质祖细胞的图案化和分化，有组织化的平滑肌细胞（SMC）和成纤维细胞的成纤维细胞产生。在这里，我们表明TBX2和TBX3转录因子具有新颖的和所需的作用，用于调节小鼠输尿管中的这些过程。在显影尿辨率的内部间充质区域中Tbx2和Tbx3的共表达需要规范wnt信号传导。该区域中TBX2 / TBX3的损失破坏了SMC程序，FOXF1和BMP4信号传导的两个关键驱动因素的活动，导致SMC分化和增加的细胞外基质增加。转录分析和染色质免疫沉淀实验表明，TBX2 / TBX3直接抑制WNT拮抗剂DKK2和SHISA2的表达，BMP拮抗剂BMP和趋化因子CXCL12。这些发现表明TBX2 / TBX3是通过在内部区域中维持BMP4和WNT信号传导的输尿管间质中促进SMC分化的典型WNT信号传导的效果，同时将CXCL12信号传导到成纤维细胞束缚的外层。

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