A dermal HOX transcriptional program regulates site-specific epidermal fate (original) (raw)

  1. John L. Rinn1,7,
  2. Jordon K. Wang1,2,7,
  3. Nancy Allen3,
  4. Samantha A. Brugmann3,
  5. Amanda J. Mikels2,4,
  6. Helen Liu1,
  7. Todd W. Ridky1,
  8. H. Scott Stadler5,
  9. Roel Nusse4,6,
  10. Jill A. Helms3, and
  11. Howard Y. Chang1,2,8
  12. 1 Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 94305, USA;
  13. 2 Cancer Biology Program, Stanford University School of Medicine, Stanford, California 94305, USA;
  14. 3 Department of Surgery, Stanford University School of Medicine, Stanford, California 94305, USA;
  15. 4 Department of Developmental Biology, Stanford University School of Medicine, Stanford, California 94305, USA;
  16. 5 Shriners Hospital for Children Research Division, Portland, Oregon 97239, USA;
  17. 6 Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305, USA
  18. ↵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.

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