Integrated β-catenin, BMP, PTEN, and Notch signalling patterns the nephron
0301 basic medicine
Notch
QH301-705.5
Science
EMC MM-04-20-01
Mice, Transgenic
PI3K
Mice
Phosphatidylinositol 3-Kinases
03 medical and health sciences
Organ Culture Techniques
BMP
Animals
Biology (General)
RNA, Small Interfering
beta Catenin
kidney development
Body Patterning
patterning
Receptors, Notch
Q
R
PTEN Phosphohydrolase
Gene Expression Regulation, Developmental
beta-catenin
Cell Differentiation
Epithelial Cells
Nephrons
Embryo, Mammalian
Developmental Biology and Stem Cells
Bone Morphogenetic Proteins
Medicine
Diffusion Chambers, Culture
Proto-Oncogene Proteins c-akt
Signal Transduction
DOI:
10.7554/elife.04000
Publication Date:
2015-02-02T15:29:34Z
AUTHORS (14)
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.
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