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 β-catenin activity along the axis of the nephron tubule. By modifying β-catenin activity, we force cells within nephrons to differentiate according to the imposed β-catenin activity level, thereby causing spatial shifts in nephron segments. The β-catenin signalling gradient interacts with the BMP pathway which, through PTEN/PI3K/AKT signalling, antagonises β-catenin activity and promotes segment identities associated with low β-catenin activity. β-catenin activity and PI3K signalling also integrate with Notch signalling to control segmentation: modulating β-catenin activity or PI3K rescues segment identities normally lost by inhibition of Notch. Our data therefore identifies a molecular network for nephron patterning.

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Keywords beta-catenin, BMP, developmental biology, kidney development, mouse, Notch, patterning, PI3K, stem cells
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Journal eLife
Lindström, N.O, Lawrence, M.L, Burn, S.F, Johansson, J.A, Bakker, E.R.M, Ridgway, R.A, … Hohenstein, P. (2014). Integrated β-catenin, BMP, PTEN, and Notch signalling patterns the nephron. eLife, 3. doi:10.7554/eLife.04000