De Novo Hair Follicle Morphogenesis and Hair Tumors in Mice Expressing a Truncated β-Catenin in Skin

Abstract

An effector of intercellular adhesion, beta-catenin also functions in Wnt signaling, associating with Lef-1/Tcf DNA-binding proteins to form a transcription factor. We report that this pathway operates in keratinocytes and that mice expressing a stabilized beta-catenin controlled by an epidermal promoter undergo a process resembling de novo hair morphogenesis. The new follicles formed sebaceous glands and dermal papilla, normally established only in embryogenesis. As in embryologically initiated hair germs, transgenic follicles induce Lef-1, but follicles are disoriented and defective in sonic hedgehog polarization. Additionally, proliferation continues unchecked, resulting in two types of tumors also found in humans. Our findings suggest that transient beta-catenin stabilization may be a key player in the long-sought epidermal signal leading to hair development and implicate aberrant beta-catenin activation in hair tumors.

Role of Pinin in neural crest, dorsal dermis, and axial skeleton development and its involvement in the regulation of Tcf/Lef activity in mice

“…Yet, the lack of mesenchymal cells derived from the dermomyotome may account for the lack of hair in the specific area. It is, of course, possible that the increase in ␤-catenin within the epidermis of the remaining body may lead to an increase in hair growth, as has been seen in other studies (Gat et al, 1998;Estrach et al, 2006).…”

Bmp signaling is required for intestinal growth and morphogenesis

“…Again, the mechanisms underlying this suppression are not clear. One possibility is that Bmp and Wnt signaling have an antagonistic function in the intestine similar to that seen in hair follicle induction in the skin, where Wnt signaling promotes and Bmp signaling inhibits hair follicle formation (Gat et al, 1998;Botchkarev et al, 1999).…”

Akt activation induces epidermal hyperplasia and proliferation of epidermal progenitors

“…The activation of Wnt/b-catenin signaling brings about similar phenotypes in adult epidermis (Gat et al, 1998;Van Mater et al, 2003;Lo Celso et al, 2004). The mice expressing stabilized b-catenin or b-cateninMer fusion protein show epidermal hyperplasia, hair follicle tumor-like outgrowth and precocious transition from telogen to anagen phase via activation of stem cells.…”