Mesenchymal-epithelial interactions in the skin: Increased expression of dickkopf1 by palmoplantar fibroblasts inhibits melanocyte growth and differentiation

Yuji Yamaguchi, Satoshi Itami, Hidenori Watabe, Ken Ichi Yasumoto, Zalfa A. Abdel-Malek, Tateki Kubo, François Rouzaud, Atsushi Tanemura, Kunihiko Yoshikawa, Vincent J. Hearing

Research output: Contribution to journalArticle

164 Citations (Scopus)

Abstract

We investigated whether or not the topographic regulation of melanocyte differentiation is determined by mesenchymal-epithelial interactions via fibroblast-derived factors. The melanocyte density in palmoplantar human skin (i.e., skin on the palms and the soles) is five times lower than that found in nonpalmoplantar sites. Palmoplantar fibroblasts significantly suppressed the growth and pigmentation of melanocytes compared with nonpalmoplantar fibroblasts. Using cDNA microarray analysis, fibroblasts derived from palmoplantar skin expressed high levels of dickkopf 1 (DKK1; an inhibitor of the canonical Wnt signaling pathway), whereas nonpalmoplantar fibroblasts expressed higher levels of DKK3. Transfection studies revealed that DKK1 decreased melanocyte function, probably through β-catenin-mediated regulation of microphthalmia-associated transcription factor activity, which in turn modulates the growth and differentiation of melanocytes. Thus, our results provide a basis to explain why skin on the palms and the soles is generally hypopigmented compared with other areas of the body, and might explain why melanocytes stop migrating in the palmoplantar area during human embryogenesis.

Original languageEnglish
Pages (from-to)275-285
Number of pages11
JournalJournal of Cell Biology
Volume165
Issue number2
DOIs
Publication statusPublished - 2004 Apr 26

Keywords

  • Dickkopf
  • MITF
  • Pigmentation
  • Regulation
  • β-catenin

ASJC Scopus subject areas

  • Cell Biology

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    Yamaguchi, Y., Itami, S., Watabe, H., Yasumoto, K. I., Abdel-Malek, Z. A., Kubo, T., Rouzaud, F., Tanemura, A., Yoshikawa, K., & Hearing, V. J. (2004). Mesenchymal-epithelial interactions in the skin: Increased expression of dickkopf1 by palmoplantar fibroblasts inhibits melanocyte growth and differentiation. Journal of Cell Biology, 165(2), 275-285. https://doi.org/10.1083/jcb.200311122