- 作者: Kan L; Liu Y; McGuire TL; Bonaguidi MA; Kessler JA
- 作者服務機構: Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago IL, USA.
- 中文摘要: --
- 英文摘要:
Background: Skin stem cells contribute to all three major lineages of epidermal appendages, i.e., the
epidermis, the hair follicle, and the sebaceous gland. In hair follicles, highly proliferative committed
progenitor cells, called matrix cells, are located at the base of the follicle in the hair bulb. The
differentiation of these early progenitor cells leads to specification of a central hair shaft surrounded by
an inner root sheath (IRS) and a companion layer. Multiple signaling molecules, including bone
morphogenetic proteins (BMPs), have been implicated in this process.
Methods: To further probe the contribution of BMP signaling to hair follicle development and
maintenance we employed a transgenic mouse that expresses the BMP inhibitor, Noggin, to disrupt
BMP signaling specifically in subset of hair follicle progenitors under the control of neuron specific
enolase (Nse) promoter. We then studied the skin tumor phenotypes of the transgenic mice through
histology, immunohistochemistry and Western Blotting to delineate the underlying mechanisms. Double
transgenic mice expressing BMP as well as noggin under control of the Nse promoter were used to
rescue the skin tumor phenotypes.
Results: We found that the transgene is expressed specifically in a subpopulation of P-cadherin positive
progenitor cells in Nse-Noggin mice. Blocking BMP signaling in this cell population led to benign hair
follicle-derived neoplasias resembling human trichofolliculomas, associated with down-regulation of Ecadherin
expression and dynamic regulation of CD44.
Conclusions: These observations further define a critical role for BMP signaling in maintaining the
homeostasis of hair follicles, and suggest that dysregulation of BMP signaling in hair follicle progenitors
may contribute to human trichofolliculoma. - 中文關鍵字: --
- 英文關鍵字: Transgenic Mice, Nse-Noggin, bone morphogenetic protein (BMP), trichofolliculoma