title: Transcriptional mechanisms link epithelial plasticity to adhesion and differentiation of epidermal progenitor cells.
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.
authors.affiliation: Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine CA 92697, USA.
authors.forename: Briana
authors.initials: B
authors.lastname: Lee
authors.affiliation: Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine CA 92697, USA.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Villarreal-Ponce
authors.affiliation: Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine CA 92697, USA.
authors.forename: Magid
authors.initials: M
authors.lastname: Fallahi
authors.affiliation: Department of Mathematics, University of California, Irvine, Irvine CA 92697, USA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Ovadia
authors.affiliation: Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine CA 92697, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Sun
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Qian-Chun
authors.initials: QC
authors.lastname: Yu
authors.affiliation: Department of Medical Chemistry, Kansai Medical University, Moriguchi 570-8506, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Ito
authors.affiliation: Department of Biochemistry, State University of New York, Buffalo, NY 14260, USA.
authors.forename: Satrajit
authors.initials: S
authors.lastname: Sinha
authors.affiliation: Department of Mathematics, University of California, Irvine, Irvine CA 92697, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Nie
authors.affiliation: Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine CA 92697, USA. Electronic address: xdai@uci.edu.
authors.forename: Xing
authors.initials: X
authors.lastname: Dai
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion; D002454:Cell Differentiation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D000078404:Epidermal Cells; D004817:Epidermis / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007365:Intercellular Junctions / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D000071799:Zinc Finger E-box-Binding Homeobox 1; D051178:alpha Catenin / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D051741:Kruppel-Like Transcription Factors; C491431:MOVO protein, mouse; C490318:Ovo1 protein, mouse; D014157:Transcription Factors; C519422:ZEB1 protein, mouse; D000071799:Zinc Finger E-box-Binding Homeobox 1; D051178:alpha Catenin
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