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
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.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (76)
CITATIONS (87)
EXTERNAL LINKS
PlumX Metrics
RECOMMENDATIONS
FAIR ASSESSMENT
Coming soon ....
JUPYTER LAB
Coming soon ....