Overexpression of Sonic Hedgehog suppresses embryonic hair follicle morphogenesis.
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.
Ellis
Tammy
T
Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
Smyth
Ian
I
Riley
Emily
E
Bowles
Josephine
J
Adolphe
Christelle
C
Rothnagel
Joseph A
JA
Wicking
Carol
C
Wainwright
Brandon J
BJ
D000818:Animals; D002280:Basal Cell Carcinoma / Q000209:etiology; D002455:Cell Division; D003598:Cytoskeletal Proteins / Q000032:analysis; D018859:Hair Follicle / Q000196:embryology*; D053823:Hedgehog Proteins; D006706:Homeostasis; D007633:Keratins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis; D012878:Skin Neoplasms / Q000209:etiology; D015534:Trans-Activators / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D053823:Hedgehog Proteins; C465570:Shh protein, mouse; D015534:Trans-Activators; D051176:beta Catenin; D007633:Keratins