| First Author | Lindström NO | Year | 2015 |
| Journal | Elife | Volume | 3 |
| Pages | e04000 | PubMed ID | 25647637 |
| Mgi Jnum | J:269494 | Mgi Id | MGI:6207273 |
| Doi | 10.7554/eLife.04000 | Citation | Lindstrom NO, et al. (2015) Integrated beta-catenin, BMP, PTEN, and Notch signalling patterns the nephron. Elife 3:e04000 |
| abstractText | The different segments of the nephron and glomerulus in the kidney balance the processes of water homeostasis, solute recovery, blood filtration, and metabolite excretion. When segment function is disrupted, a range of pathological features are presented. Little is known about nephron patterning during embryogenesis. In this study, we demonstrate that the early nephron is patterned by a gradient in beta-catenin activity along the axis of the nephron tubule. By modifying beta-catenin activity, we force cells within nephrons to differentiate according to the imposed beta-catenin activity level, thereby causing spatial shifts in nephron segments. The beta-catenin signalling gradient interacts with the BMP pathway which, through PTEN/PI3K/AKT signalling, antagonises beta-catenin activity and promotes segment identities associated with low beta-catenin activity. beta-catenin activity and PI3K signalling also integrate with Notch signalling to control segmentation: modulating beta-catenin activity or PI3K rescues segment identities normally lost by inhibition of Notch. Our data therefore identifies a molecular network for nephron patterning. |
