Development of hair follicles, mammary glands, taste papillae and teeth; regeneration and neogenesis of hair follicles and teeth; hair follicle, mammary gland and dental stem cells; skin and mammary gland tumorigenesis; microRNA functions in embryonic and postnatal skin and mammary glands; functions of histone deacetylases in skin and hair follicle development and renewal.
hair, stem cells, regeneration, skin, tooth, mammary gland, mouse, Wnt, Bmp, beta-catenin, Dicer, miRNA, HDAC, chromatin.
Description of Research
Our research is focused on understanding cell-cell signaling mechanisms controlling development, stem cell function and regeneration of the epidermis and organs such as hair follicles, mammary glands, taste papillae and teeth that arise from embryonic ectoderm (ectodermal appendages). We have shown that Wnt/beta-catenin signaling is required for initiating the formation of hair follicles, mammary glands and taste papillae from multipotent cells in the embryonic surface ectoderm, and plays key roles in regulating the functions of adult epithelial stem cells. We are currently using genetic approaches to determine how Wnt signaling is regulated and patterned within the skin, and are utilizing activation of this pathway in strategies for organ regeneration. We are using genetic approaches to identify Wnt ligands and receptors required for appendage development, and to investigate the roles played by non-beta-catenin mediated Wnt signaling in the skin. We are also interested in epigenetic mechanisms controlling development, differentiation, regeneration and tumorigenesis. Currently, we are investigating the mechanisms by which histone deacetylases control self-renewal and differentiation of skin stem cells, and are probing the roles of specific HDAC family members in skin tumorigenesis.
1. Dissection of mechanisms controlling patterning of ectodermal appendages using live imaging and genetic approaches
2. HDAC functions in skin development, stem cells and cancer
3. Identification of Wnt ligands and inhibitors regulating skin stem cell functions
Fang Liu, Ph.D., Post-doctoral Fellow
Mingang Xu, Ph.D., Research Associate
Xuming Zhu, Post-doctoral fellow
Emma Sung, Graduate Student
Heather Gochnauer, Lab Manager
Hannah Sweeney, Undergraduate Student
Jeremy Horrell, Post-bac student
Andl, T., Reddy S. T., Gaddapara, T. & Millar, S. E. : WNT signals are required for the initiation of hair follicle development. Developmental Cell 2: 643-653, 2002.
Chu, E. Y., Hens, J., Andl, T., Kairo, A., Yamaguchi, T. P., Brisken, C., Glick, A., Wysolmerski, J. J., & Millar, S. E. : Canonical WNT signaling promotes mammary placode development and is essential for initiation of mammary gland morphogenesis. Development 131: 4819-4829, 2004.
Andl, T., Murchison, E. P., Liu, F., Zhang, Y., Yunta-Gonzalez, M., Tobias, J. W., Andl, C, D., Seykora, J. T., Hannon, G. J., Millar, S. E.: The miRNA processing enzyme Dicer is essential for the morphogenesis and maintenance of hair follicles. Current Biology 6: 1041-9, 2006.
Liu, F., Thirumangalathu, S., Gallant, N. M., Yang, S. H., Stoick-Cooper, C. L., Reddy, S. T., Andl, T., Taketo, M. M., Dlugosz, A. A., Moon, R. T., Barlow, L. A., Millar, S. E.: Wnt-beta-catenin signaling initiates taste papilla development. Nat Genet. 39: 106-12, 2007.
Zhang, Y., Andl, T., Yang, S.H., Teta, M., Liu, F., Seykora, J.T., Tobias, J.W., Piccolo, S., Schmidt-Ullrich, R., Nagy, A., Taketo, M.M., Dlugosz, A.A., Millar, S.E.: Activation of beta-catenin signaling programs embryonic epidermis to hair follicle fate. Development 135: 2161-72, June 2008 Notes: Highlighted paper. Epub 2008 May 14.
Zhang Y, Tomann P, Andl T, Gallant NM, Huelsken J, Jerchow B, Birchmeier W, Paus R, Piccolo S, Mikkola ML, Morrisey EE, Overbeek P, Scheidereit C, Millar SE*, Schmidt-Ullrich R*. [*Joint last and corresponding authors.]: Reciprocal requirements for Eda/Edar/NF-kappa B and Wnt/b-catenin signaling pathways in hair follicle induction. Developmental Cell 17, 49-61 2009.
Liu F, Dangaria S, Andl T, Zhang Y, Wright A C, Damek-Poprawa M, Piccolo S, Nagy A, Taketo M M, Diekwisch T G H, Akintoye S O, Millar S E: beta-Catenin initiates tooth neogenesis in adult rodent incisors. Journal of Dental Research 89(9): 909-14, Sep 2010.
LeBoeuf Matthew, Terrell Anne, Trivedi Sohum, Sinha Satrajit, Epstein Jonathan A, Olson Eric N, Morrisey Edward E, Millar Sarah E: Hdac1 and Hdac2 act redundantly to control p63 and p53 functions in epidermal progenitor cells. Developmental Cell 19(6): 807-18, Dec 2010.
Teta Monica, Choi Yeon Sook, Okegbe Tishina, Wong Gabrielle, Tam Oliver H, Chong Mark M W, Seykora John T, Nagy Andras, Littman Dan R, Andl Thomas, Millar Sarah E: Inducible deletion of epidermal Dicer and Drosha reveals multiple functions for miRNAs in postnatal skin. Development (Cambridge, England) 139(8): 1405-16, Apr 2012.
Choi Yeon Sook, Zhang Yuhang, Xu Mingang, Yang Yongguang, Ito Mayumi, Peng Tien, Cui Zheng, Nagy Andras, Hadjantonakis Anna-Katerina, Lang Richard A, Cotsarelis George, Andl Thomas, Morrisey Edward E, Millar Sarah E: Distinct functions for Wnt/β-catenin in hair follicle stem cell proliferation and survival and interfollicular epidermal homeostasis. Cell stem cell 13(6): 720-33, Dec 2013 Notes: Subject of a Preview Article in Cell Stem Cell: Morgan BA. (2013). The "skinny" on Wnt signaling in stem cells. Cell Stem Cell 13, 638-40.
-Subject of a Preview Article in Science: Frede J, Jones PH. (2013).
Development. Permission to proliferate. Science 342, 1183-4.
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Last updated: 01/27/2017
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