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Curr Biol. 2008 Apr 8;18(7):507-13. doi: 10.1016/j.cub.2008.02.076.

Cell-polarity dynamics controls the mechanism of lumen formation in epithelial morphogenesis.

Author information

1
Centro de Biología Molecular Severo-Ochoa, CSIC, Universidad Autónoma de Madrid, Madrid 28049, Spain. fmartin@cbm.uam.es

Erratum in

  • Curr Biol. 2008 Apr 22;18(8):630. Ewald, Andrew [corrected to Ewald, Andrew J].
  • Curr Biol. 2008 Jul 8;18(13):1016.

Abstract

Many organs consist of tubes of epithelial cells enclosing a central lumen. How the space of this lumen is generated is a key question in morphogenesis. Two predominant mechanisms of de novo lumen formation have been observed: hollowing and cavitation. In hollowing, the lumen is formed by exocytosis and membrane separation, whereas, in cavitation, the lumen is generated by apoptosis of cells in the middle of the structure [1, 2]. Using MDCK cells in three-dimensional cultures, we found an inverse correlation between polarization efficiency and apoptosis. When cells were grown in collagen, where cells polarized slowly, apoptosis was needed for lumen formation. However, in the presence of Matrigel, which allowed rapid polarization, lumens formed without apoptosis. If polarization in Matrigel was perturbed by blocking formation of the apical surface by RNAi of Cdc42, lumens formed by apoptosis. In a complementary approach, we plated cells at high density so that aggregates formed with little polarity. These aggregates required apoptosis to form lumens, whereas cells plated at low density formed cysts with rapidly polarizing cells and did not need apoptosis to form lumens. The mechanism of lumen formation in the 3D-MDCK model can shift between hollowing and cavitation, depending on cell polarization.

PMID:
18394894
PMCID:
PMC2405957
DOI:
10.1016/j.cub.2008.02.076
[Indexed for MEDLINE]
Free PMC Article

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