Overexpression of Sonic Hedgehog suppresses embryonic hair follicle morphogenesis

Dev Biol. 2003 Nov 15;263(2):203-15. doi: 10.1016/s0012-1606(03)00394-4.

Abstract

The Sonic Hedgehog (Shh) signalling pathway plays a central role in the development of the skin and hair follicle and is a major determinant of skin tumorigenesis, most notably of basal cell carcinoma (BCC). Various mouse models involving either ablation or overexpression of key members of the Shh signalling pathway display a range of skin tumours. To further examine the role of Shh in skin development, we have overexpressed Shh in a subset of interfollicular basal cells from 12.5 dpc under the control of the human keratin 1 (HK1) promoter. The HK1-Shh transgenic mice display a range of skin anomalies, including highly pigmented inguinal lesions and regions of alopecia. The most striking hair follicle phenotype is a suppression in embryonic follicle development between 14.0 and 19.0 dpc, resulting in a complete absence of guard, awl, and auchene hair fibres. These data indicate that alternative signals are responsible for the development of different hair follicles and point to a major role of Shh signalling in the morphogenesis of guard, awl, and auchene hair fibres. Through a comparison with other mouse models, the characteristics of the HK1-Shh transgenic mice suggest that the precise timing and site of Shh expression are key in dictating the resultant skin and tumour phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Basal Cell / etiology
  • Cell Division
  • Cytoskeletal Proteins / analysis
  • Hair Follicle / embryology*
  • Hedgehog Proteins
  • Homeostasis
  • Keratins / genetics
  • Mice
  • Mice, Transgenic
  • Morphogenesis
  • Skin Neoplasms / etiology
  • Trans-Activators / analysis
  • Trans-Activators / genetics
  • Trans-Activators / physiology*
  • beta Catenin

Substances

  • CTNNB1 protein, mouse
  • Cytoskeletal Proteins
  • Hedgehog Proteins
  • Shh protein, mouse
  • Trans-Activators
  • beta Catenin
  • Keratins