Impaired skin and hair follicle development in Runx2 deficient mice

Dev Biol. 2008 Mar 15;315(2):459-73. doi: 10.1016/j.ydbio.2008.01.005. Epub 2008 Jan 16.

Abstract

The transcription factor, Runx2, is known to play crucial roles in skeletal and tooth morphogenesis. Here we document that Runx2 has a regulatory role in skin and hair follicle development. The expression of Runx2 is restricted to hair follicles and is dynamic, pari passu with follicle development. Follicle maturation is delayed in the absence of Runx2 and overall skin and epidermal thickness of Runx2 null embryos is significantly reduced. The Runx2 null epidermis is hypoplastic, displaying reduced expression of Keratin 14, Keratin 1 and markers of proliferation. The expression pattern of Runx2 in the bulb epithelium of mature hair follicles is asymmetric and strikingly similar to that of Sonic hedgehog. This suggests that Runx2 may be a regulator of hedgehog signaling in skin as it is in bones and teeth. Supporting this possibility, we demonstrate that Sonic hedgehog, Patched1 and Gli1 transcripts are reduced in the skin of Runx2 null embryos. Moreover, we document Patched1 expression in epidermal basal cells and show that the skin of Sonic(+/-) embryos is thinner than that of wild-type littermates. These observations suggest that Runx2 and hedgehog signaling are involved in the well known, but unexplained, coupling of skin thickness to hair follicle development.

Publication types

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

MeSH terms

  • Animals
  • Core Binding Factor Alpha 1 Subunit / deficiency*
  • Core Binding Factor Alpha 1 Subunit / genetics
  • Core Binding Factor Alpha 1 Subunit / physiology
  • Female
  • Gene Expression Regulation, Developmental
  • Hair Follicle / abnormalities
  • Hair Follicle / embryology*
  • Hair Follicle / metabolism
  • Hedgehog Proteins / deficiency
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / physiology
  • Keratin-14 / metabolism
  • Lac Operon
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Patched Receptors
  • Patched-1 Receptor
  • Pregnancy
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / physiology
  • Signal Transduction / physiology
  • Skin / embryology*
  • Skin / metabolism
  • Skin Abnormalities / embryology
  • Skin Abnormalities / genetics
  • Skin Abnormalities / metabolism
  • Skin Transplantation
  • Transplantation, Homologous

Substances

  • Core Binding Factor Alpha 1 Subunit
  • Hedgehog Proteins
  • Keratin-14
  • Krt14 protein, mouse
  • Patched Receptors
  • Patched-1 Receptor
  • Ptch1 protein, mouse
  • Receptors, Cell Surface
  • Runx2 protein, mouse
  • Shh protein, mouse