Integrated β-catenin, BMP, PTEN, and Notch signalling patterns the nephron

Nils Lindstrom, Melanie L Lawrence, Sally F Burn, Jeanette A Johansson, Elvira Rm Bakker, Rachel A Ridgway, C-hong Chang, Michele J Karolak, Leif Oxburgh, Denis J Headon, Owen J Sansom, Ron Smits, Jamie A Davies, Peter Hohenstein

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Article numbere04000
Publication statusPublished - 3 Feb 2015


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