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Building epithelial architecture: insights from three-dimensional culture models

Nature Reviews Molecular Cell Biology volume 3, pages 531–537 (2002)Cite this article

Abstract

How do individual cells organize into multicellular tissues? Here, we propose that the morphogenetic behaviour of epithelial cells is guided by two distinct elements: an intrinsic differentiation programme that drives formation of a lumen-enclosing monolayer, and a growth factor-induced, transient de-differentiation that allows this monolayer to be remodelled.

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Figure 1: The building blocks of epithelial organs.
Figure 2: MDCK cyst morphology mimics epithelial organization in vivo.
Figure 3: Cyst development and the generation of three membrane surfaces.
Figure 4: Tubulogenetic mechanisms in MDCK cells.
Figure 5: The drive for three surfaces and EMT specify epithelial architecture.
Figure 6: Other tubulogenetic mechanisms.

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Acknowledgements

We thank J. Thaler and A. Datta for helpful comments, and we are grateful to our colleagues who shared data with us before publication. L.E.O. is supported by an NIH training grant. M.M.P.Z. was supported by California ACS. Work in our lab is supported by NIH grants to K.E.M.

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Authors and Affiliations

  1. the Department of Anatomy, Department of Biochemistry and Biophysics, and the Cardiovascular Research Institute, University of California, San Francisco, 94143, California, USA

    Lucy Erin O'Brien, Mirjam M. P. Zegers & Keith E. Mostov

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  1. Lucy Erin O'Brien
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  2. Mirjam M. P. Zegers
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  3. Keith E. Mostov
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Correspondence to Keith E. Mostov.

Supplementary information

Movie of elongating and collapsing HGF-induced extensions

Movie. Alternating phases of growth and collapse characterize HGF-induced extension formation (AVI 692 kb)

Phase-contrast images taken at 15-minute intervals over an 8 hour period show hepatocyte growth factor (HGF)-induced extension formation to be dynamic. Individual extensions grow and collapse through a sequence of events reminiscent of neuronal growth cone pathfinding. In some instances, several rounds of growth and collapse were observed. In other cases, the tip of the extension exhibited small lateral movements, as though it was 'probing' the extracellular matrix. A minority of extensions appeared stable throughout the period of image acquisition. On occasion, developing extensions appeared to pull the entire cell body away from the cyst. These detached cells retracted their extensions and rounded up.

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Flybase

Par-3

Par-6

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APC

Bcl-2

cyclin D1

ErbB2

HGF

MUC1

Rac1

Sec10

<i>Saccharomyces</i> Genome Database

Sec6

Sec8

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β-catenin

MT1-MMP

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Par-1

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O'Brien, L., Zegers, M. & Mostov, K. Building epithelial architecture: insights from three-dimensional culture models. Nat Rev Mol Cell Biol 3, 531–537 (2002). https://doi.org/10.1038/nrm859

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