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

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