| First Author | Nie X | Year | 2011 |
| Journal | Dev Biol | Volume | 352 |
| Issue | 1 | Pages | 141-51 |
| PubMed ID | 21281623 | Mgi Jnum | J:171473 |
| Mgi Id | MGI:4949995 | Doi | 10.1016/j.ydbio.2011.01.027 |
| Citation | Nie X, et al. (2011) Six1 regulates Grem1 expression in the metanephric mesenchyme to initiate branching morphogenesis. Dev Biol 352(1):141-51 |
| abstractText | 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. |
