p120 catenin is required for normal renal tubulogenesis and glomerulogenesis

Denise K. Marciano, Paul R. Brakeman, Chao Zong Lee, Natalie Spivak, Dennis J. Eastburn, David M. Bryant, Gerard M. Beaudoin, Ilse Hofmann, Keith E. Mostov, Louis F. Reichardt

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Defects in the development or maintenance of tubule diameter correlate with polycystic kidney disease. Here, we report that absence of the cadherin regulator p120 catenin (p120ctn) from the renal mesenchyme prior to tubule formation leads to decreased cadherin levels with abnormal morphologies of early tubule structures and developing glomeruli. In addition, mutant mice develop cystic kidney disease, with markedly increased tubule diameter and cellular proliferation, and detached luminal cells only in proximal tubules. The p120ctn homolog Arvcf is specifically absent from embryonic proximal tubules, consistent with the specificity of the proximal tubular phenotype. p120ctn knockdown in renal epithelial cells in 3D culture results in a similar cystic phenotype with reduced levels of E-cadherin and active RhoA. We find that E-cadherin knockdown, but not RhoA inhibition, phenocopies p120ctn knockdown. Taken together, our data show that p120ctn is required for early tubule and glomerular morphogenesis, as well as control of luminal diameter, probably through regulation of cadherins.

Original languageEnglish (US)
Pages (from-to)2099-2109
Number of pages11
JournalDevelopment
Volume138
Issue number10
DOIs
StatePublished - May 1 2011

Keywords

  • Cadherins
  • Glomerulogenesis
  • Kidney development
  • Mouse
  • Polycystic disease
  • p120 catenin

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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  • Cite this

    Marciano, D. K., Brakeman, P. R., Lee, C. Z., Spivak, N., Eastburn, D. J., Bryant, D. M., Beaudoin, G. M., Hofmann, I., Mostov, K. E., & Reichardt, L. F. (2011). p120 catenin is required for normal renal tubulogenesis and glomerulogenesis. Development, 138(10), 2099-2109. https://doi.org/10.1242/dev.056564