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.
Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
Tammy
T
Ellis
Ian
I
Smyth
Emily
E
Riley
Josephine
J
Bowles
Christelle
C
Adolphe
Joseph A
JA
Rothnagel
Carol
C
Wicking
Brandon J
BJ
Wainwright
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