Cell-cell communication is essential to the development and function of the skin and its appendages. We discovered that the canonical WNT/beta-catenin intercellular signaling pathway is required for initiating the formation of all types of hair follicle placodes during embryogenesis, and is essential postnatally for hair growth. These findings have potential significance for the development of strategies for regenerating hair follicles in cases of congenital absence or loss, and for the treatment of hair growth disorders. However, as activating mutations in beta-catenin can cause hair follicle tumors, it will be of critical importance to delineate the precise mechanisms by which WNT/beta-catenin signals normally initiate hair follicle development and regulate postnatal hair growth, and to identify the WNT ligands that control normal development and growth. To these ends we will test the hypothesis that WNT/beta-catenin signaling initiates hair follicle morphogenesis by direct activation of genes of the tumor necrosis factor (TNF) and TNF receptor familes. We will manipulate WNT/beta-catenin signaling in inducible transgenic mouse models to determine the requirement for this pathway for the onset and maintenance of the anagen phase of the hair growth cycle, and we will examine the skin phenotypes of mice mutant for two hair follicle-expressed Wnt genes. Unexpectedly, we discovered that expression of Frizzled WNT receptors in developing and postnatal skin is not confined to sites of known activity of the WNT/beta-catenin pathway, suggesting that WNT signaling through alternate pathways may contribute to the development and maintenance of the skin and hair follicles. Non-canonical WNT signaling regulates the planar cell polarity of epithelial cells and cell movements in vertebrate embryos. We will test the hypothesis that non-canonical WNT signaling is important for cell movements and polarity in skin epithelia by depleting the function of a key non-canonical WNT signaling pathway component in mouse skin in vivo and in cultured keratinocyes. ? ?

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
Project #
Application #
Study Section
Arthritis, Connective Tissue and Skin Study Section (ACTS)
Program Officer
Baker, Carl
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Pennsylvania
Schools of Medicine
United States
Zip Code
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