Dkk4 and Eda regulate distinctive developmental mechanisms for subtypes of mouse hair

PLoS One. 2010 Apr 1;5(4):e10009. doi: 10.1371/journal.pone.0010009.

Abstract

The mouse hair coat comprises protective "primary" and thermo-regulatory "secondary" hairs. Primary hair formation is ectodysplasin (Eda) dependent, but it has been puzzling that Tabby (Eda(-/y)) mice still make secondary hair. We report that Dickkopf 4 (Dkk4), a Wnt antagonist, affects an auxiliary pathway for Eda-independent development of secondary hair. A Dkk4 transgene in wild-type mice had no effect on primary hair, but secondary hairs were severely malformed. Dkk4 action on secondary hair was further demonstrated when the transgene was introduced into Tabby mice: the usual secondary follicle induction was completely blocked. The Dkk4-regulated secondary hair pathway, like the Eda-dependent primary hair pathway, is further mediated by selective activation of Shh. The results thus reveal two complex molecular pathways that distinctly regulate subtype-based morphogenesis of hair follicles, and provide a resolution for the longstanding puzzle of hair formation in Tabby mice lacking Eda.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Ectodysplasins / physiology*
  • Hair / growth & development*
  • Hair Follicle / growth & development
  • Hedgehog Proteins / metabolism
  • Intercellular Signaling Peptides and Proteins / physiology*
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Morphogenesis

Substances

  • Dkk4 protein, mouse
  • Ectodysplasins
  • Eda protein, mouse
  • Hedgehog Proteins
  • Intercellular Signaling Peptides and Proteins
  • Shh protein, mouse