Formation of Multicellular Epithelial Structures

  1. Gregory Bock Organizer and
  2. Jamie Goode
  1. Keith Mostov1,2,
  2. Paul Brakeman2,
  3. Anirban Datta2,
  4. Ama Gassama2,
  5. Leonid Katz2,
  6. Minji Kim2,
  7. Pascale Leroy2,
  8. Max Levin2,
  9. Kathleen Liu2,
  10. Fernando Martin2,
  11. Lucy E. O'Brien2,
  12. Marcel Verges2,
  13. Tao Su2,
  14. Kitty Tang2,
  15. Naoki Tanimizu2,
  16. Toshiyuki Yamaji2 and
  17. Wei Yu2

Published Online: 7 OCT 2008

DOI: 10.1002/047001766X.ch15

Signalling Networks in Cell Shape and Motility: Novartis Foundation Symposium 269

Signalling Networks in Cell Shape and Motility: Novartis Foundation Symposium 269

How to Cite

Mostov, K., Brakeman, P., Datta, A., Gassama, A., Katz, L., Kim, M., Leroy, P., Levin, M., Liu, K., Martin, F., O'Brien, L. E., Verges, M., Su, T., Tang, K., Tanimizu, N., Yamaji, T. and Yu, W. (2005) Formation of Multicellular Epithelial Structures, in Signalling Networks in Cell Shape and Motility: Novartis Foundation Symposium 269 (eds G. Bock and J. Goode), John Wiley & Sons, Ltd, Chichester, UK. doi: 10.1002/047001766X.ch15

Author Information

  1. 1

    Genentech Hall, Room N212B, Box 2140, 600 16th Street, San Francisco, CA 94143-2140, USA

  2. 2

    Department of Anatomy, and Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143-2140, USA

Publication History

  1. Published Online: 7 OCT 2008
  2. Published Print: 9 SEP 2005

Book Series:

  1. Novartis Foundation Symposia

Book Series Editors:

  1. Novartis Foundation

ISBN Information

Print ISBN: 9780470011904

Online ISBN: 9780470017661

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Keywords:

  • epithelial polarization;
  • SNARE proteins;
  • syntaxin 2;
  • dominant negative (DN) Rac1;
  • tetracycline-repressible system;
  • cell–cell contact;
  • laminin assembly;
  • orientation of cyst polarity

Summary

The kidney is primarily comprised of highly polarized epithelial cells. Much has been learned recently about the mechanisms of epithelial polarization. However, in most experimental systems the orientation of this polarity is determined by external cues, such as growth of epithelial cells on a filter support. When Madin-Darby canine kidney (MDCK) cells are grown instead in a three-dimensional (3D) collagen gel, the cells form hollow cysts lined by a monolayer of epithelial cells, with their apical surfaces all facing the central lumen. We have found that expression of a dominant-negative (DN) form of the small GTPase Rac1 causes an inversion of epithelial polarity, such that the apical surface of the cells instead faces the periphery of the cyst. This indicates that the establishment of polarity and the orientation of polarity can be experimentally separated by growing cells in a 3D collagen gel, where there is no filter support to provide an external cue for orientation. DN Rac1 causes a defect in the assembly of laminin into its normal basement membrane network, and addition of a high concentration of exogenous laminin rescues the inversion of polarity caused by DN Rac1.