title: YAP regulates the expression of Hoxa1 and Hoxc13 in mouse and human oral and skin epithelial tissues.
abstract: Yes-associated protein (YAP) is a Hippo signaling transcriptional coactivator that plays pivotal roles in stem cell proliferation, organ size control, and tumor development. The downstream targets of YAP have been shown to be highly context dependent. In this study, we used the embryonic mouse tooth germ as a tool to search for the downstream targets of YAP in ectoderm-derived tissues. Yap deficiency in the dental epithelium resulted in a small tooth germ with reduced epithelial cell proliferation. We compared the gene expression profiles of embryonic day 14.5 (E14.5) Yap conditional knockout and YAP transgenic mouse tooth germs using transcriptome sequencing (RNA-Seq) and further confirmed the differentially expressed genes using real-time PCR and in situ hybridization. We found that YAP regulates the expression of Hoxa1 and Hoxc13 in oral and dental epithelial tissues as well as in the epidermis of skin during embryonic and adult stages. Sphere formation assay suggested that Hoxa1 and Hoxc13 are functionally involved in YAP-regulated epithelial progenitor cell proliferation, and chromatin immunoprecipitation (ChIP) assay implies that YAP may regulate Hoxa1 and Hoxc13 expression through TEAD transcription factors. These results provide mechanistic insights into abnormal YAP activities in mice and humans.
authors.affiliation: Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts, USA Department of Pediatric Dentistry, School of Stomatology, Peking University, Beijing, China.
authors.forename: Shuangyun
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts, USA Department of Implantation, School of Stomatology, Shandong University, Jinan, China.
authors.forename: Qingjie
authors.initials: Q
authors.lastname: Lin
authors.affiliation: Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts, USA xwang2527@gmail.com.
authors.forename: Xiu-Ping
authors.initials: XP
authors.lastname: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D018797:Cell Cycle Proteins; D002460:Cell Line; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009061:Mouth Mucosa / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D014070:Tooth / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D000091102:YAP-Signaling Proteins; D000099261:Homeobox A1 Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D018398:Homeodomain Proteins; D010750:Phosphoproteins; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; D000099261:Homeobox A1 Protein; C410305:HOXC13 protein, human; C485834:Hoxc13 protein, mouse; C088374:YAP1 protein, human; C486223:Yap1 protein, mouse