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

TY - JOUR

T1 - Cdc42 is crucial for the establishment of epithelial polarity during early mammalian development.

AU - Wu, Xunwei

AU - Li, Shaohua

AU - Chrostek-Grashoff, Anna

AU - Czuchra, Aleksandra

AU - Meyer, Hannelore

AU - Yurchenco, Peter D

AU - Brakebusch, Cord

N1 - Keywords: Adherens Junctions; Animals; Basement Membrane; Cadherins; Catenins; Cell Polarity; Embryonic Stem Cells; Epithelial Cells; Mice; Protein Kinase C; Repressor Proteins; Tight Junctions; cdc42 GTP-Binding Protein; rac1 GTP-Binding Protein; rhoA GTP-Binding Protein

PY - 2007

Y1 - 2007

N2 - 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 GSK3beta, and a diminished activity of Rac1. However, neither Rac1 nor the kinase function of GSK3beta seem to contribute to cell polarization and cell-cell contacts. In contrast, EBs expressing dominant-negative (dn) PKCzeta 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 PKCzeta-dependent regulation of the protein levels of p120 catenin and E-cadherin.

AB - 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 GSK3beta, and a diminished activity of Rac1. However, neither Rac1 nor the kinase function of GSK3beta seem to contribute to cell polarization and cell-cell contacts. In contrast, EBs expressing dominant-negative (dn) PKCzeta 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 PKCzeta-dependent regulation of the protein levels of p120 catenin and E-cadherin.

U2 - 10.1002/dvdy.21309

DO - 10.1002/dvdy.21309

M3 - Journal article

C2 - 17849438

SN - 1058-8388

VL - 236

SP - 2767

EP - 2778

JO - Developmental Dynamics

JF - Developmental Dynamics

IS - 10

ER -