Cdc42 is crucial for the establishment of epithelial polarity during early mammalian development

Xunwei Wu, Shaohua Li, Anna Chrostek-Grashoff, Aleksandra Czuchra, Hannelore Meyer, Peter Yurchenco, Cord Brakebusch

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

To study the role of Cdc42 in the establishment of epithelial polarity during mammalian development, we generated murine Cdc42-null embryonic stem cells and analyzed peri-implantation development using embryoid bodies (EBs). Mutant EBs developed endoderm and underlying basement membrane, but exhibited defects of cell polarity, cell-cell junctions, survival, and cavitation. These defects corresponded to a decreased phosphorylation and membrane localization of aPKC, a reduced phosphorylation of GSK3β, and a diminished activity of Rac1. However, neither Rac1 nor the kinase function of GSK3β seem to contribute to cell polarization and cell-cell contacts. In contrast, EBs expressing dominant-negative (dn) PKCζ mimicked well the phenotype of Cdc42-null EBs, suggesting a major role of aPKC in mediating cell polarization downstream of Cdc42. Finally, aggregation experiments with endodermal cell lines suggested that Cdc42 might affect formation of adherens and tight junctions by PKCζ-dependent regulation of the protein levels of p120 catenin and E-cadherin.

Original languageEnglish (US)
Pages (from-to)2767-2778
Number of pages12
JournalDevelopmental Dynamics
Volume236
Issue number10
DOIs
StatePublished - Oct 1 2007

Fingerprint

Embryoid Bodies
Phosphorylation
Adherens Junctions
Cell Polarity
Endoderm
Intercellular Junctions
Tight Junctions
Cadherins
Embryonic Stem Cells
Basement Membrane
Cell Survival
Phosphotransferases
Phenotype
Cell Line
Membranes

All Science Journal Classification (ASJC) codes

  • Developmental Biology

Keywords

  • Cdc42
  • Embryoid bodies
  • Epithelial polarity

Cite this

Wu, Xunwei ; Li, Shaohua ; Chrostek-Grashoff, Anna ; Czuchra, Aleksandra ; Meyer, Hannelore ; Yurchenco, Peter ; Brakebusch, Cord. / Cdc42 is crucial for the establishment of epithelial polarity during early mammalian development. In: Developmental Dynamics. 2007 ; Vol. 236, No. 10. pp. 2767-2778.
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Cdc42 is crucial for the establishment of epithelial polarity during early mammalian development. / Wu, Xunwei; Li, Shaohua; Chrostek-Grashoff, Anna; Czuchra, Aleksandra; Meyer, Hannelore; Yurchenco, Peter; Brakebusch, Cord.

In: Developmental Dynamics, Vol. 236, No. 10, 01.10.2007, p. 2767-2778.

Research output: Contribution to journalArticle

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