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

Document Type

Article

Publication Date

2-3-2015

Institution/Department

Molecular Medicine; MMCRI

Journal Title

eLife

MeSH Headings

Animals, Body Patterning, Bone Morphogenetic Proteins, Cell Differentiation, Diffusion Chambers, Culture, Embryo, Mammalian, Epithelial Cells, Gene Expression Regulation, Developmental, Mice, Mice, Transgenic, Nephrons, Organ Culture Techniques, PTEN Phosphohydrolase, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-akt, RNA, Small Interfering, Receptors, Notch, Signal Transduction, beta Catenin

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.

ISSN

2050-084X

First Page

04000

Last Page

04000

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