1] Department of Internal Medicine (Nephrology), University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9148, USA [2] Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9148, USA.
Nat Cell Biol. 2013 Sep;15(9):1035-44. doi: 10.1038/ncb2828. Epub 2013 Aug 25.
Present models suggest that the fate of the kidney epithelial progenitors is solely regulated by signals from the adjacent ureteric bud. The bud provides signals that regulate the survival, renewal and differentiation of these cells. Recent data suggest that Wnt9b, a ureteric-bud-derived factor, is sufficient for both progenitor cell renewal and differentiation. How the same molecule induces two seemingly contradictory processes is unknown. Here, we show that signals from the stromal fibroblasts cooperate with Wnt9b to promote differentiation of the progenitors. The atypical cadherin Fat4 encodes at least part of this stromal signal. Our data support a model whereby proper kidney size and function is regulated by balancing opposing signals from the ureteric bud and stroma to promote renewal and differentiation of the nephron progenitors.
目前的模型表明，肾脏上皮祖细胞的命运仅受来自相邻输尿管芽的信号调控。芽提供的信号调节这些细胞的存活、更新和分化。最近的数据表明，输尿管芽衍生的因子 Wnt9b 足以促进祖细胞的更新和分化。同一分子如何诱导两种看似矛盾的过程尚不清楚。在这里，我们表明来自基质成纤维细胞的信号与 Wnt9b 合作促进祖细胞的分化。非典型钙黏蛋白 Fat4 至少编码了部分这种基质信号。我们的数据支持这样一种模型，即通过平衡输尿管芽和基质的相反信号来促进肾单位祖细胞的更新和分化，从而调节适当的肾脏大小和功能。
