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

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 ?-catenin activity along the axis of the nephron tubule. By modifying ?-catenin activity, we force cells within nephrons to differentiate according to the imposed ?-catenin activity level, thereby causing spatial shifts in nephron segments. The ?-catenin signalling gradient interacts with the BMP pathway which, through PTEN/PI3K/AKT signalling, antagonises ?-catenin activity and promotes segment identities associated with low ?-catenin activity. ?-catenin activity and PI3K signalling also integrate with Notch signalling to control segmentation: modulating ?-catenin activity or PI3K rescues segment identities normally lost by inhibition of Notch. Our data therefore identifies a molecular network for nephron patterning.

SUBMITTER: Lindstrom NO 

PROVIDER: S-EPMC4337611 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature