An Ovol2-Zeb1 transcriptional circuit regulates epithelial directional migration and proliferation

Journal article


Publication Details

Author(s): Haensel D, Sun P, Maclean AL, Ma X, Zhou Y, Stemmler M, Brabletz S, Berx G, Plikus MV, Nie Q, Brabletz T, Dai X
Journal: EMBO Reports
Publication year: 2019
Volume: 20
Journal issue: 1
ISSN: 1469-221X
eISSN: 1469-3178


Abstract

Directional migration is inherently important for epithelial tissue regeneration and repair, but how it is precisely controlled and coordinated with cell proliferation is unclear. Here, we report that Ovol2, a transcriptional repressor that inhibits epithelial-to-mesenchymal transition (EMT), plays a crucial role in adult skin epithelial regeneration and repair. Ovol2-deficient mice show compromised wound healing characterized by aberrant epidermal cell migration and proliferation, as well as delayed anagen progression characterized by defects in hair follicle matrix cell proliferation and subsequent differentiation. Epidermal keratinocytes and bulge hair follicle stem cells (Bu-HFSCs) lacking Ovol2 fail to expand in culture and display molecular alterations consistent with enhanced EMT and reduced proliferation. Live imaging of wound explants and Bu-HFSCs reveals increased migration speed but reduced directionality, and post-mitotic cell cycle arrest. Remarkably, simultaneous deletion of Zeb1 encoding an EMT-promoting factor restores directional migration to Ovol2-deficient Bu-HFSCs. Taken together, our findings highlight the important function of an Ovol2-Zeb1 EMT-regulatory circuit in controlling the directional migration of epithelial stem and progenitor cells to facilitate adult skin epithelial regeneration and repair.


FAU Authors / FAU Editors

Brabletz, Thomas Prof. Dr. med.
Lehrstuhl für Experimentelle Medizin mit dem Schwerpunkt Molekulare Pathogeneseforschung
Brabletz, Simone PD Dr.
Lehrstuhl für Experimentelle Medizin II (Molekulare Tumorforschung)
Stemmler, Marc PD Dr.
Lehrstuhl für Experimentelle Medizin mit dem Schwerpunkt Molekulare Pathogeneseforschung


External institutions with authors

Universiteit Gent (UGent) / Ghent University
University of California Irvine


How to cite

APA:
Haensel, D., Sun, P., Maclean, A.L., Ma, X., Zhou, Y., Stemmler, M.,... Dai, X. (2019). An Ovol2-Zeb1 transcriptional circuit regulates epithelial directional migration and proliferation. EMBO Reports, 20(1). https://dx.doi.org/10.15252/embr.201846273

MLA:
Haensel, Daniel, et al. "An Ovol2-Zeb1 transcriptional circuit regulates epithelial directional migration and proliferation." EMBO Reports 20.1 (2019).

BibTeX: 

Last updated on 2019-23-07 at 08:53