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Elife. 2015 Feb 3;3:e04000. doi: 10.7554/eLife.04000.

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

Author information

1
Division of Developmental Biology, The Roslin Institute, University of Edinburgh, Easter Bush, United Kingdom.
2
Centre for Integrated Physiology, University of Edinburgh, Edinburgh, United Kingdom.
3
Department of Genetics and Development, Columbia University, New York, United States.
4
Laboratory of Gastroenterology and Hepatology, Erasmus MC, University Medical Centre, Rotterdam, Netherlands.
5
Department of Invasion and Metastasis, Cancer Research UK Beatson Institute, Glasgow, United Kingdom.
6
Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, United States.
7
Beatston Institute for Cancer Research, Glasgow, United Kingdom.

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.

KEYWORDS:

BMP; Notch; PI3K; beta-catenin; developmental biology; kidney development; mouse; patterning; stem cells

PMID:
25647637
PMCID:
PMC4337611
DOI:
10.7554/eLife.04000
[Indexed for MEDLINE]
Free PMC Article

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