A dermal HOX transcriptional program regulates site-specific epidermal fate.
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.
Rinn
John L
JL
Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
Wang
Jordon K
JK
Allen
Nancy
N
Brugmann
Samantha A
SA
Mikels
Amanda J
AJ
Liu
Helen
H
Ridky
Todd W
TW
Stadler
H Scott
HS
Nusse
Roel
R
Helms
Jill A
JA
Chang
Howard Y
HY
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
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