Cell-Polarity Dynamics Controls the Mechanism of Lumen Formation in Epithelial Morphogenesis

Fernando Martín-Belmonte, Wei Yu, Alejo E. Rodríguez-Fraticelli, Andrew Ewald, Zena Werb, Miguel A. Alonso, Keith Mostov

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)507-513
Number of pages7
JournalCurrent Biology
Volume18
Issue number7
DOIs
StatePublished - Apr 8 2008
Externally publishedYes

Fingerprint

Cell Polarity
Morphogenesis
morphogenesis
Apoptosis
apoptosis
Cavitation
Polarization
cells
cell aggregates
Madin Darby Canine Kidney Cells
Exocytosis
RNA Interference
cell polarity
exocytosis
Cysts
Collagen
collagen
Epithelial Cells
epithelial cells
Membranes

Keywords

  • DEVBIO

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

Cite this

Martín-Belmonte, F., Yu, W., Rodríguez-Fraticelli, A. E., Ewald, A., Werb, Z., Alonso, M. A., & Mostov, K. (2008). Cell-Polarity Dynamics Controls the Mechanism of Lumen Formation in Epithelial Morphogenesis. Current Biology, 18(7), 507-513. https://doi.org/10.1016/j.cub.2008.02.076

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 journalArticle

Martín-Belmonte, F, Yu, W, Rodríguez-Fraticelli, AE, Ewald, A, Werb, Z, Alonso, MA & Mostov, K 2008, 'Cell-Polarity Dynamics Controls the Mechanism of Lumen Formation in Epithelial Morphogenesis', Current Biology, vol. 18, no. 7, pp. 507-513. https://doi.org/10.1016/j.cub.2008.02.076
Martín-Belmonte F, Yu W, Rodríguez-Fraticelli AE, Ewald A, Werb Z, Alonso MA et al. Cell-Polarity Dynamics Controls the Mechanism of Lumen Formation in Epithelial Morphogenesis. Current Biology. 2008 Apr 8;18(7):507-513. https://doi.org/10.1016/j.cub.2008.02.076
Martín-Belmonte, Fernando ; Yu, Wei ; Rodríguez-Fraticelli, Alejo E. ; Ewald, Andrew ; Werb, Zena ; Alonso, Miguel A. ; Mostov, Keith. / Cell-Polarity Dynamics Controls the Mechanism of Lumen Formation in Epithelial Morphogenesis. In: Current Biology. 2008 ; Vol. 18, No. 7. pp. 507-513.
@article{f927205a8d864c5797803661cdaa572a,
title = "Cell-Polarity Dynamics Controls the Mechanism of Lumen Formation in Epithelial Morphogenesis",
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.",
keywords = "DEVBIO",
author = "Fernando Mart{\'i}n-Belmonte and Wei Yu and Rodr{\'i}guez-Fraticelli, {Alejo E.} and Andrew Ewald and Zena Werb and Alonso, {Miguel A.} and Keith Mostov",
year = "2008",
month = "4",
day = "8",
doi = "10.1016/j.cub.2008.02.076",
language = "English (US)",
volume = "18",
pages = "507--513",
journal = "Current Biology",
issn = "0960-9822",
publisher = "Cell Press",
number = "7",

}

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

VL - 18

SP - 507

EP - 513

JO - Current Biology

JF - Current Biology

SN - 0960-9822

IS - 7

ER -