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- W2021661525 abstract "Urinary tract morphogenesis requires subdivision of the ureteric bud (UB) into the intra-renal collecting system and the extra-renal ureter, by responding to signals in its surrounding mesenchyme. BMP4 is a mesenchymal regulator promoting ureter development, while GREM1 is necessary to negatively regulate BMP4 activity to induce UB branching. However, the mechanisms that regulate the GREM1-BMP4 signaling are unknown. Previous studies have shown that Six1-deficient mice lack kidneys, but form ureters. Here, we show that the tip cells of Six1−/− UB fail to form an ampulla for branching. Instead, the UB elongates within Tbx18- and Bmp4-expressing mesenchyme. We find that the expression of Grem1 in the metanephric mesenchyme (MM) is Six1-dependent. Treatment of Six1−/− kidney rudiments with GREM1 protein restores ampulla formation and branching morphogenesis. Furthermore, we demonstrate that genetic reduction of BMP4 levels in Six1−/− (Six1−/−; Bmp4+/−) embryos restores urinary tract morphogenesis and kidney formation. This study uncovers an essential function for Six1 in the MM as an upstream regulator of Grem1 in initiating branching morphogenesis." @default.
- W2021661525 created "2016-06-24" @default.
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- W2021661525 date "2011-04-01" @default.
- W2021661525 modified "2023-10-16" @default.
- W2021661525 title "Six1 regulates Grem1 expression in the metanephric mesenchyme to initiate branching morphogenesis" @default.
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- W2021661525 doi "https://doi.org/10.1016/j.ydbio.2011.01.027" @default.
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