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Article

  • The EMBO Journal (2005) 24, 1146 - 1156
  • doi:10.1038/sj.emboj.7600605

Published online: 3 March 2005

E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions

Judith A Tunggal1,a, Iris Helfrich1,a, Annika Schmitz1, Heinz Schwarz2, Dorothee Günzel3, Michael Fromm3, Rolf Kemler4, Thomas Krieg1,5 and Carien M Niessen1

  1. Center for Molecular Medicine, University of Cologne (CMMC), Cologne, Germany
  2. Max Planck Institute for Developmental Biology, Tuebingen, Germany
  3. Department of Clinical Physiology, Charité, Campus Benjamin Franklin, Berlin, Germany
  4. Department of Molecular Embryology, Max Planck Institute for Immunobiology, Freiburg, Germany
  5. Department of Dermatology, University of Cologne, Cologne, Germany

Correspondence to:

Carien M Niessen, Center for Molecular Medicine (ZMMK), University of Cologne, LFI, 05, room 59, Joseph Stelzmannstrasse 9, 50931 Cologne, Germany. Tel.: +221 4787738; Fax: +221 4784836; E-mail: carien.niessen@uni-koeln.de

aThese authors contributed equally to this work

Received 29 October 2004; Accepted 8 February 2005

Cadherin adhesion molecules are key determinants of morphogenesis and tissue architecture. Nevertheless, the molecular mechanisms responsible for the morphogenetic contributions of cadherins remain poorly understood in vivo. Besides supporting cell–cell adhesion, cadherins can affect a wide range of cellular functions that include activation of cell signalling pathways, regulation of the cytoskeleton and control of cell polarity. To determine the role of E-cadherin in stratified epithelium of the epidermis, we have conditionally inactivated its gene in mice. Here we show that loss of E-cadherin in the epidermis in vivo results in perinatal death of mice due to the inability to retain a functional epidermal water barrier. Absence of E-cadherin leads to improper localization of key tight junctional proteins, resulting in permeable tight junctions and thus altered epidermal resistance. In addition, both Rac and activated atypical PKC, crucial for tight junction formation, are mislocalized. Surprisingly, our results indicate that E-cadherin is specifically required for tight junction, but not desmosome, formation and this appears to involve signalling rather than cell contact formation.

  • Keywords:

    • E-cadherin,
    • epidermal barrier,
    • gene targeting,
    • polarity,
    • tight junctions