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

Lindström, N. O. et al. (2015) Integrated β-catenin, BMP, PTEN, and notch signalling patterns the nephron. eLife, 4, e04000. (doi:10.7554/eLife.04000) (PMID:25647637) (PMCID:4337611)

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Abstract

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Ridgway, Dr Rachel and Sansom, Professor Owen
Authors: Lindström, N. O., Lawrence, M. L., Burn, S. F., Johansson, J. A., Bakker, E. R.M., Ridgway, R., Chang, C.-H., Karolak, M. J., Oxburgh, L., Headon, D. J., Sansom, O. J., Smits, R., Davies, J. A., and Hohenstein, P.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:eLife
Publisher:eLife Sciences Publications
ISSN:2050-084X
ISSN (Online):2050-084X
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in eLife 4:e04000
Publisher Policy:Reproduced under a Creative Commons License

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