title: A dermal HOX transcriptional program regulates site-specific epidermal fate.
abstract: Reciprocal epithelial-mesenchymal interactions shape site-specific development of skin. Here we show that site-specific HOX expression in fibroblasts is cell-autonomous and epigenetically maintained. The distal-specific gene HOXA13 is continually required to maintain the distal-specific transcriptional program in adult fibroblasts, including expression of WNT5A, a morphogen required for distal development. The ability of distal fibroblasts to induce epidermal keratin 9, a distal-specific gene, is abrogated by depletion of HOXA13, but rescued by addition of WNT5A. Thus, maintenance of appropriate HOX transcriptional program in adult fibroblasts may serve as a source of positional memory to differentially pattern the epithelia during homeostasis and regeneration.
authors.affiliation: Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: John L
authors.initials: JL
authors.lastname: Rinn
authors.forename: Jordon K
authors.initials: JK
authors.lastname: Wang
authors.forename: Nancy
authors.initials: N
authors.lastname: Allen
authors.forename: Samantha A
authors.initials: SA
authors.lastname: Brugmann
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Mikels
authors.forename: Helen
authors.initials: H
authors.lastname: Liu
authors.forename: Todd W
authors.initials: TW
authors.lastname: Ridky
authors.forename: H Scott
authors.initials: HS
authors.lastname: Stadler
authors.forename: Roel
authors.initials: R
authors.lastname: Nusse
authors.forename: Jill A
authors.initials: JA
authors.lastname: Helms
authors.forename: Howard Y
authors.initials: HY
authors.lastname: Chang
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D004817:Epidermis / Q000196:embryology* / Q000378:metabolism; D044127:Epigenesis, Genetic; D004848:Epithelium / Q000196:embryology / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000378:metabolism*; D007633:Keratins / Q000378:metabolism; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*; D000071818:Wnt-5a Protein
chemical_list: D018398:Homeodomain Proteins; D011518:Proto-Oncogene Proteins; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C438615:Wnt5a protein, mouse; C099959:homeobox protein HOXA13; D007633:Keratins