title: Ablation of coactivator Med1 switches the cell fate of dental epithelia to that generating hair.
abstract: Cell fates are determined by specific transcriptional programs. Here we provide evidence that the transcriptional coactivator, Mediator 1 (Med1), is essential for the cell fate determination of ectodermal epithelia. Conditional deletion of Med1 in vivo converted dental epithelia into epidermal epithelia, causing defects in enamel organ development while promoting hair formation in the incisors. We identified multiple processes by which hairs are generated in Med1 deficient incisors: 1) dental epithelial stem cells lacking Med 1 fail to commit to the dental lineage, 2) Sox2-expressing stem cells extend into the differentiation zone and remain multi-potent due to reduced Notch1 signaling, and 3) epidermal fate is induced by calcium as demonstrated in dental epithelial cell cultures. These results demonstrate that Med1 is a master regulator in adult stem cells to govern epithelial cell fate.
authors.affiliation: Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Keigo
authors.initials: K
authors.lastname: Yoshizaki
authors.affiliation: Departments of Medicine and Endocrinology, University of California San Francisco and Veterans Affairs Medical Center San Francisco, San Francisco, California, United States of America.
authors.forename: Lizhi
authors.initials: L
authors.lastname: Hu
authors.affiliation: Departments of Medicine and Endocrinology, University of California San Francisco and Veterans Affairs Medical Center San Francisco, San Francisco, California, United States of America.
authors.forename: Thai
authors.initials: T
authors.lastname: Nguyen
authors.affiliation: Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Sakai
authors.affiliation: Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Bing
authors.initials: B
authors.lastname: He
authors.affiliation: Departments of Medicine and Endocrinology, University of California San Francisco and Veterans Affairs Medical Center San Francisco, San Francisco, California, United States of America.
authors.forename: Chak
authors.initials: C
authors.lastname: Fong
authors.affiliation: Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Departments of Medicine and Endocrinology, University of California San Francisco and Veterans Affairs Medical Center San Francisco, San Francisco, California, United States of America.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Bikle
authors.affiliation: Departments of Medicine and Endocrinology, University of California San Francisco and Veterans Affairs Medical Center San Francisco, San Francisco, California, United States of America.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Oda
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D004847:Epithelial Cells / Q000166:cytology*; D004848:Epithelium / Q000254:growth & development; D006197:Hair / Q000166:cytology / Q000254:growth & development*; D006801:Humans; D007180:Incisor / Q000166:cytology / Q000254:growth & development; D056913:Mediator Complex Subunit 1 / Q000235:genetics*; D051379:Mice; D038081:Organogenesis; D055153:Stem Cell Niche; D013234:Stem Cells
chemical_list: C538856:Med1 protein, mouse; D056913:Mediator Complex Subunit 1