A dermal HOX transcriptional program regulates site-specific epidermal fate
- John L. Rinn1,7,
- Jordon K. Wang1,2,7,
- Nancy Allen3,
- Samantha A. Brugmann3,
- Amanda J. Mikels2,4,
- Helen Liu1,
- Todd W. Ridky1,
- H. Scott Stadler5,
- Roel Nusse4,6,
- Jill A. Helms3, and
- Howard Y. Chang1,2,8
- 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
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↵7 These authors contributed equally to this work.
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.
Keywords
Footnotes
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↵8 Corresponding author.
↵8 E-MAIL howchang{at}stanford.edu; FAX (650) 723-8762.
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Supplemental material is available at http://www.genesdev.org.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1610508
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- Received August 29, 2007.
- Accepted December 3, 2007.
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Freely available online through the Genes & Development Open Access option.
- Copyright © 2008, Cold Spring Harbor Laboratory Press
