(Verbatim) Many key intercellular signals required for hair follicle morphogenesis in the embryo and cyclical hair growth in the adult remain unidentified at the molecular level. It is already well established that inappropriate activation of follicular intercellular signaling pathways can cause tumors and hair loss. Therefore identification of the signaling molecules and receptors that operate in hair follicles will provide us with a better understanding of the molecular events underlying pathogenic states in the skin and may ultimately permit the development of novel therapies. Published data and our Preliminary Studies suggest specific WNT proteins as strong candidates for several of these signals. The goals of this proposal are to test the hypothesis that WNT proteins convey information between follicular epithelial cells and between the follicular epithelium and the mesenchyme, and that this dialog is required for the normal development and function of hair follicles. To test this hypothesis we will: (1) Define the profile of WNT receptor (Frizzled) gene expression in developing and mature hair follicles; (2) Determine the effects of blocking interactions between WNT proteins and their Frizzled receptors in the epidermis in vivo; (3) Determine the effects on skin and hair development of loss of function mutations in two Wnt genes that are expressed at key stages in hair follicle development and hair growth; and (4) Determine the roles of WNT signaling in the dermal component of the hair follicle by creating a null mutation in an essential effector of WNT signaling, specifically within this compartment. Understanding the roles of these key signaling molecules in developing and mature skin will provide us with new insight into normal skin and hair follicle biology and disease states including hair loss diseases and skin cancers.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
1R01AR047709-01
Application #
6320422
Study Section
General Medicine A Subcommittee 2 (GMA)
Program Officer
Moshell, Alan N
Project Start
2001-04-01
Project End
2006-02-28
Budget Start
2001-04-01
Budget End
2002-02-28
Support Year
1
Fiscal Year
2001
Total Cost
$396,250
Indirect Cost
Name
University of Pennsylvania
Department
Dermatology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Millar, Sarah E (2015) Secrets of the Hair Follicle: Now on Your iPhone. Dev Cell 34:488-90
Choi, Yeon Sook; Zhang, Yuhang; Xu, Mingang et al. (2013) Distinct functions for Wnt/?-catenin in hair follicle stem cell proliferation and survival and interfollicular epidermal homeostasis. Cell Stem Cell 13:720-33
Plikus, Maksim V; Baker, Ruth E; Chen, Chih-Chiang et al. (2011) Self-organizing and stochastic behaviors during the regeneration of hair stem cells. Science 332:586-9
LeBoeuf, Matthew; Terrell, Anne; Trivedi, Sohum et al. (2010) Hdac1 and Hdac2 act redundantly to control p63 and p53 functions in epidermal progenitor cells. Dev Cell 19:807-18
Liu, F; Dangaria, S; Andl, T et al. (2010) beta-Catenin initiates tooth neogenesis in adult rodent incisors. J Dent Res 89:909-14
Osada, Masako; Jardine, Logan; Misir, Ruth et al. (2010) DKK1 mediated inhibition of Wnt signaling in postnatal mice leads to loss of TEC progenitors and thymic degeneration. PLoS One 5:e9062
Liu, F; Millar, S E (2010) Wnt/beta-catenin signaling in oral tissue development and disease. J Dent Res 89:318-30
Zhang, Yuhang; Tomann, Philip; Andl, Thomas et al. (2009) Reciprocal requirements for EDA/EDAR/NF-kappaB and Wnt/beta-catenin signaling pathways in hair follicle induction. Dev Cell 17:49-61
Zhang, Yuhang; Andl, Thomas; Yang, Steven H et al. (2008) Activation of beta-catenin signaling programs embryonic epidermis to hair follicle fate. Development 135:2161-72
Yang, Steven Hoseong; Andl, Thomas; Grachtchouk, Vladimir et al. (2008) Pathological responses to oncogenic Hedgehog signaling in skin are dependent on canonical Wnt/beta3-catenin signaling. Nat Genet 40:1130-5

Showing the most recent 10 out of 19 publications