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

Elife 2015 Feb 3;3:e04000. Epub 2015 Feb 3.

Division of Developmental Biology, The Roslin Institute, University of Edinburgh, Easter Bush, United Kingdom.

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.

Download full-text PDF

Source
https://elifesciences.org/articles/04000
Publisher Site
http://dx.doi.org/10.7554/eLife.04000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4337611PMC
February 2015
30 Reads

Publication Analysis

Top Keywords

β-catenin activity
28
β-catenin
8
nephron segments
8
activity pi3k
8
segment identities
8
notch signalling
8
nephron patterning
8
nephron
7
activity
7
signalling
5
axis nephron
4
signalling integrate
4
β-catenin bmp
4
nephron tubule
4
activity axis
4
modifying β-catenin
4
activity β-catenin
4
force cells
4
activity force
4
tubule modifying
4

Similar Publications