Transcriptional Mechanisms Link Epithelial Plasticity to Adhesion and Differentiation of Epidermal Progenitor Cells
Authors
Briana Lee, Alvaro Villarreal-Ponce, Magid Fallahi, Jeremy Ovadia, Peng Sun, Qian-Chun Yu, Seiji Ito, Satrajit Sinha, Qing Nie, and Xing Dai
Institution
UC Irvine
Country
United States
Year
2014
Journal
Developmental Cell
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 a-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-
a-catenin sequential repression and highlight Ovol1
and Ovol2 as gatekeepers of epithelial adhesion and
differentiation by inhibiting progenitor-like traits and
epithelial plasticity.