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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 507-513 |
| Number of pages | 7 |
| Journal | Current Biology |
| Volume | 18 |
| Issue number | 7 |
| DOIs | |
| State | Published - Apr 8 2008 |
| Externally published | Yes |
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Keywords
- DEVBIO
ASJC Scopus subject areas
- Agricultural and Biological Sciences(all)
Cite this
Cell-Polarity Dynamics Controls the Mechanism of Lumen Formation in Epithelial Morphogenesis. / Martín-Belmonte, Fernando; Yu, Wei; Rodríguez-Fraticelli, Alejo E.; Ewald, Andrew; Werb, Zena; Alonso, Miguel A.; Mostov, Keith.
In: Current Biology, Vol. 18, No. 7, 08.04.2008, p. 507-513.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cell-Polarity Dynamics Controls the Mechanism of Lumen Formation in Epithelial Morphogenesis
AU - Martín-Belmonte, Fernando
AU - Yu, Wei
AU - Rodríguez-Fraticelli, Alejo E.
AU - Ewald, Andrew
AU - Werb, Zena
AU - Alonso, Miguel A.
AU - Mostov, Keith
PY - 2008/4/8
Y1 - 2008/4/8
N2 - 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.
AB - 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.
KW - DEVBIO
UR - http://www.scopus.com/inward/record.url?scp=41449087759&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=41449087759&partnerID=8YFLogxK
U2 - 10.1016/j.cub.2008.02.076
DO - 10.1016/j.cub.2008.02.076
M3 - Article
C2 - 18394894
AN - SCOPUS:41449087759
VL - 18
SP - 507
EP - 513
JO - Current Biology
JF - Current Biology
SN - 0960-9822
IS - 7
ER -