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

Haensel D, Sun P, Maclean AL, Ma X, Zhou Y, Stemmler M, Brabletz S, Berx G, Plikus MV, Nie Q, Brabletz T, Dai X (2019)


Publication Type: Journal article

Publication year: 2019

Journal

Book Volume: 20

Article Number: e46273

Journal Issue: 1

DOI: 10.15252/embr.201846273

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.

Authors with CRIS profile

Involved external institutions

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: Download