Cdc42 regulates epithelial cell polarity and cytoskeletal function during kidney tubule development

Bertha C. Elias, Amrita Das, Diptiben V. Parekh, Glenda Mernaugh, Rebecca Adams, Zhufeng Yang, Cord Brakebusch, Ambra Pozzi, Denise K. Marciano, Thomas J. Carroll, Roy Zent

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

The Rho GTPase Cdc42 regulates key signaling pathways required for multiple cell functions, including maintenance of shape, polarity, proliferation, migration, differentiation and morphogenesis. Although previous studies have shown that Cdc42 is required for proper epithelial development and maintenance, its exact molecular function in kidney development is not well understood. In this study, we define the specific role of Cdc42 during murine kidney epithelial tubulogenesis by deleting it selectively at the initiation of ureteric bud or metanephric mesenchyme development. Deletion in either lineage results in abnormal tubulogenesis, with profound defects in polarity, lumen formation and the actin cytoskeleton. Ultimately, these defects lead to renal failure. Additionally, in vitro analysis of Cdc42-null collecting duct cells shows that Cdc42 controls these processes by regulating the polarity Par complex (Par3-Par6-aPKC-Cdc42) and the cytoskeletal proteins N-Wasp and ezrin. Thus, we conclude that the principal role of Cdc42 in ureteric bud and metanephric mesenchyme development is to regulate epithelial cell polarity and the actin cytoskeleton.

Original languageEnglish (US)
Pages (from-to)4293-4305
Number of pages13
JournalJournal of Cell Science
Volume128
Issue number23
DOIs
StatePublished - 2015

Keywords

  • Epithelial cell
  • GTPase
  • Metanephric mesenchyme
  • Signaling
  • Ureteric bud

ASJC Scopus subject areas

  • Cell Biology

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    Elias, B. C., Das, A., Parekh, D. V., Mernaugh, G., Adams, R., Yang, Z., Brakebusch, C., Pozzi, A., Marciano, D. K., Carroll, T. J., & Zent, R. (2015). Cdc42 regulates epithelial cell polarity and cytoskeletal function during kidney tubule development. Journal of Cell Science, 128(23), 4293-4305. https://doi.org/10.1242/jcs.164509