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

Nils Lindstrom*, Melanie L. Lawrence, Sally F. Burn, Jeanette A. Johansson, Elvira Rm Bakker, Rachel A. Ridgway, C. Hong Chang, Michele J. Karolak, Leif Oxburgh, Denis J. Headon, Owen J. Sansom, Ron Smits, Jamie A. Davies, Peter Hohenstein

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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.

Original languageEnglish (US)
Article numbere04000
Pages (from-to)1-29
Number of pages29
JournaleLife
Volume2015
Issue number4
DOIs
StatePublished - Mar 2 2015

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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