Department of Urology, Yale University School of Medicine, New Haven, CT 06520, USA.
J Am Soc Nephrol. 2013 Mar;24(4):618-26. doi: 10.1681/ASN.2012090902. Epub 2013 Feb 28.
Developing and adult ureters express the epigenetic regulator Brg1, but the role of Brg1 in ureter development is not well understood. We conditionally ablated Brg1 in the developing ureter using Hoxb7-Cre and found that Brg1 expression is upstream of p63, Pparγ, and sonic hedgehog (Shh) expression in the ureteral epithelium. In addition, epithelial stratification in the basal cells required Brg1-dependent p63 expression, whereas terminal differentiation of the umbrella cells required Brg1-dependent Pparγ expression. Furthermore, the loss of ureteric Brg1 resulted in failure of Shh expression, which correlated with reduced smooth muscle cell development and hydroureter. Taken together, we conclude that Brg1 expression unifies three aspects of ureter development: maintenance of the basal cell population, guidance for terminal differentiation of urothelial cells, and proper investment of ureteral smooth muscle cells.
发育中的输尿管和成人输尿管表达表观遗传调节剂 Brg1，但 Brg1 在输尿管发育中的作用尚不清楚。我们使用 Hoxb7-Cre 条件性敲除发育中的输尿管中的 Brg1，发现 Brg1 表达在上皮细胞中 p63、Pparγ 和 sonic hedgehog (Shh) 表达的上游。此外，基底细胞中的上皮分层需要 Brg1 依赖性 p63 表达，而伞细胞的终末分化需要 Brg1 依赖性 Pparγ 表达。此外，输尿管 Brg1 的缺失导致 Shh 表达失败，这与平滑肌细胞发育不良和肾盂积水有关。综上所述，我们得出结论，Brg1 表达统一了输尿管发育的三个方面：维持基底细胞群体、指导尿路上皮细胞的终末分化以及输尿管平滑肌细胞的适当投资。
