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RESEARCH COMMUNICATION

A dermal HOX transcriptional program regulates site-specific epidermal fate

¹ Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 94305, USA; ² Cancer Biology Program, Stanford University School of Medicine, Stanford, California 94305, USA; ³ Department of Surgery, Stanford University School of Medicine, Stanford, California 94305, USA; ⁴ Department of Developmental Biology, Stanford University School of Medicine, Stanford, California 94305, USA; ⁵ Shriners Hospital for Children Research Division, Portland, Oregon 97239, USA; ⁶ Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305, USA

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.

[Keywords: HOXA13; WNT5A; chromatin immunoprecipitation; gene regulation; epithelial–mesenchymal interaction]]

Received August 29, 2007; revised version accepted December 3, 2007.

⁸ Corresponding author.

E-MAIL howchang{at}stanford.edu; FAX (650) 723-8762.

Supplemental material is available at http://www.genesdev.org.

Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1610508

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