A Wnt7b-dependent pathway regulates the orientation of epithelial cell division and establishes the cortico-medullary axis of the mammalian kidney

Jing Yu, Thomas J. Carroll, Jay Rajagopal, Akio Kobayashi, Qun Ren, Andrew P. McMahon

Research output: Contribution to journalArticle

153 Scopus citations

Abstract

The mammalian kidney is organized into a cortex where primary filtration occurs, and a medullary region composed of elongated tubular epithelia where urine is concentrated. We show that the cortico-medullary axis of kidney organization and function is regulated by Wnt7b signaling. The future collecting duct network specifically expresses Wnt7b. In the absence of Wnt7b, cortical epithelial development is normal but the medullary zone fails to form and urine fails to be concentrated normally. The analysis of cell division planes in the collecting duct epithelium of the emerging medullary zone indicates a bias along the longitudinal axis of the epithelium. By contrast, in Wnt7b mutants, cell division planes in this population are biased along the radial axis, suggesting that Wnt7b-mediated regulation of the cell cleavage plane contributes to the establishment of a cortico-medullary axis. The removal of β-catenin from the underlying Wnt-responsive interstitium phenocopies the medullary deficiency of Wnt7b mutants, suggesting a paracrine role for Wnt7b action through the canonical Wnt pathway. Wnt7b signaling is also essential for the coordinated growth of the loop of Henle, a medullary extension of the nephron that elongates in parallel to the collecting duct epithelium. These findings demonstrate that Wnt7b is a key regulator of the tissue architecture that establishes a functional physiologically active mammalian kidney.

Original languageEnglish (US)
Pages (from-to)161-171
Number of pages11
JournalDevelopment
Volume136
Issue number1
DOIs
StatePublished - Apr 14 2009

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Keywords

  • Collecting duct elongation
  • Loop of Henle elongation
  • Mouse
  • Oriented cell division
  • Renal cortico-medullary axis
  • Renal medulla
  • Wnt7b

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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