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Dev Cell. 2014 Apr 14;29(1):47-58. doi: 10.1016/j.devcel.2014.03.005.

Transcriptional mechanisms link epithelial plasticity to adhesion and differentiation of epidermal progenitor cells.

Author information

1
Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine CA 92697, USA.
2
Department of Mathematics, University of California, Irvine, Irvine CA 92697, USA.
3
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
4
Department of Medical Chemistry, Kansai Medical University, Moriguchi 570-8506, Japan.
5
Department of Biochemistry, State University of New York, Buffalo, NY 14260, USA.
6
Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine CA 92697, USA. Electronic address: xdai@uci.edu.

Abstract

During epithelial tissue morphogenesis, developmental progenitor cells undergo dynamic adhesive and cytoskeletal remodeling to trigger proliferation and migration. Transcriptional mechanisms that restrict such a mild form of epithelial plasticity to maintain lineage-restricted differentiation in committed epithelial tissues are poorly understood. Here, we report that simultaneous ablation of transcriptional repressor-encoding Ovol1 and Ovol2 results in expansion and blocked terminal differentiation of embryonic epidermal progenitor cells. Conversely, mice overexpressing Ovol2 in their skin epithelia exhibit precocious differentiation accompanied by smaller progenitor cell compartments. We show that Ovol1/Ovol2-deficient epidermal cells fail to undertake α-catenin-driven actin cytoskeletal reorganization and adhesive maturation and exhibit changes that resemble epithelial-to-mesenchymal transition (EMT). Remarkably, these alterations and defective terminal differentiation are reversed upon depletion of EMT-promoting transcriptional factor Zeb1. Collectively, our findings reveal Ovol-Zeb1-α-catenin sequential repression and highlight Ovol1 and Ovol2 as gatekeepers of epithelial adhesion and differentiation by inhibiting progenitor-like traits and epithelial plasticity.

PMID:
24735878
PMCID:
PMC4153751
DOI:
10.1016/j.devcel.2014.03.005
[Indexed for MEDLINE]
Free PMC Article

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