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Signaling to Structures: Skin Appendages, Development and Diseases — Meeting Report of the 55th Annual Montagna Symposium on the Biology of Skin

      Approximately 120 participants gathered for the 55th Annual Montagna Symposium on the Biology of Skin.
      The 55th Annual Montagna Symposium on the Biology of Skin was held at Salishan Resort, Gleneden Beach, Oregon, USA, 12–16 October 2006.
      Information about content and support of past Symposia and the next Montagna Symposium on the Biology of Skin can be foundat http://www.montagnasymposium.org/.
      *The 55th Annual Montagna Symposium on the Biology of Skin was held at Salishan Resort, Gleneden Beach, Oregon, USA, 12–16 October 2006.Information about content and support of past Symposia and the next Montagna Symposium on the Biology of Skin can be foundat http://www.montagnasymposium.org/.
      Presentations by 22 invited speakers, seven short talks chosen from submitted abstracts, and 37 posters were heard and discussed.
      This meeting continues to follow the tradition established in 1950 by Dr. William Montagna. It is a forum where basic cutaneous biologists and clinically trained scientists meet with practicing clinicians to discuss a single major topic in cutaneous biology. The topic for the 55th Annual Montagna Symposium was “Signaling to Structures: Skin Appendages, Development and Diseases.” The flow of presentations led the discussion from basic aspects of skin biology to clinical challenges and potential opportunities. This included plenary sessions with vibrant discussions and breakout sessions where we discussed topics necessary to advance this research.
      The three program chairs, Sarah E. Millar, PhD, George Cotsarelis, MD (both from University of Pennsylvania Medical School, Philadelphia, PA), and Andrzej A. Dlugosz, MD (University of Michigan Comprehensive Cancer Center, Ann Arbor, MI), put together an exciting program, beginning with a keynote talk by Pierre Coulombe (Johns Hopkins University, Baltimore, MD), who discussed the roles of keratin 17 in appendages, including the exciting finding that keratin 17 is upregulated in basal-cell carcinoma and may be a target of Gli2.
      Hair Follicle/Sebaceous Gland. Ralf Paus (University of Lübeck, Germany) began with an overview of the hair follicle, which included a discussion of the hair follicle’s immune privilege and how this is broken down in autoimmune disease. Raphael Kopan (Washington University, St. Louis, MO) followed with a presentation of how notch-1 and transforming growth factor-β control theG1-to-S cell-cycle phase transition of epidermal and mesenchymal cells in hair follicles. Diane Thiboutot (Pennsylvania State University College of Medicine, Hershey) gave an overview of the sebaceous gland and acne. Her take-home message was that we need better FDA-approved ways to reduce sebaceous production and thereby reduce acne. Vladimir Botchkarev (Boston University School of Medicine, Boston, MA) followed with a discussion of the signaling of bone morphogenic proteins (BMPs) in hair follicles of various sizes. Angela Christiano (Columbia University, New York, NY) presented findings that high expression of P-cadherin directly relates to down-growth of hair follicles during development and to the sparsity of hair in diseases such as juvenile muscular dystrophy.
      Integument Appendages: Beyond Hair. The topic of this session was non-hair appendages. John Wysolmerski (Yale University School of Medicine, New Haven, CT) began by explaining that expression of parathyroid hormone-related protein (PTHrP) first in the epithelial cells, then in the mesenchymal cells, is required for mammary gland morphogenesis. Marja Mikkola (University of Helsinki, Finland) gave a short talk concerning her findings that mutated Eda-1, found in ectodermal dysplasia, results in the failure of molar cusps to form properly on teeth. Cynthia Loomis (New York University School of Medicine, New York, NY) followed with her studies showing that engrailed (En-1) is required for proper formation of nails, even in adults. Continuing this theme, Vu Nguyen (University of Pennsylvania, Philadelphia) described his studies using the zebrafish model to discover genes required for scales of teeth formation, and Benjamin Yu (University of California, San Francisco) gave a short talk on sprouty and its requirement for hand formation.
      Stem Cells in Appendages. George Cotsarelis (University of Pennsylvania, Philadelphia) discussed the role of hair follicle bulge stem cells in wound healing. Weimin Zhong (Yale University, New Haven, CT) compared the expression of Numb in brain and hair follicle development. Carol Trempus (National Institute of Environmental Health Sciences, Research Triangle Park, NC) gave a short talk on her findings that CD34-positive bulge cells were the targets of chemical carcinogenic inducers. Fiona Watt (Cancer Research UK Cambridge Research Institute, Cambridge) used an inducible mouse model to determine that β-catenin signaled before notch was activated in hair follicle formation. Sarah Millar (University of Pennsylvania, Philadelphia) used the BAT-gal reporter mouse model to determine that the ectopic expression of DKK1 inhibited formation of all appendages. James Rheinwald (Brigham and Women’s Hospital and Harvard Medical School, Boston, MA) gave a short presentation on his findings that keratinocytes must bypass p16 to become immortalized. Luis Garza’s (University of Pennsylvania, Philadelphia) short talk described his findings that balding human scalp skin appeared to maintain stem cells, even though it had no hair. Ian Mackenzie (Institute of Cell and Molecular Science, London, UK) ended the session by discussing the maintenance of stem-cell patterns in tumor cultures.
      Dr. Frances Storrs, Professor Emerita, Oregon Health and Science University (Portland), gave a sometimes hilarious, sometimes serious presentation of what life as a practicing dermatologist was like, from being a resident attending the Symposia on the Biology of Skin in Montagna’s time up until this meeting, where she enjoyed a standing ovation for her synopsis of the meeting through puns on the names of genes discussed.
      Epidermis/Mesenchyme. Cheng-Ming Chuong (University of Southern California, Los Angeles) compared feather formation to hair formation and discussed his findings that regulation of BMPs and fibroblast growth factor-10 controls the amount of stalk and branches of the feathers. Howard Chang (Stanford University, Palo Alto, CA) followed with a discussion on how the pattern of genes expressed in fibroblasts determined distal–proximal, anterior–posterior, and interior–exterior axes. Bruce Morgan (Harvard Medical School, Boston) presented his data concerning the after-determination of the mesenchymal cells in and around the hair follicle. In short talks, Radhika Atit (Case Western Reserve University, Cleveland) presented that β-catenin was required for somites to make dorsal dermis, and Beatrice Howard (Breakthrough Breast Cancer Research Center, London, UK) presented that neuregulin 3 was required for somites to form nipples.
      The signaling theme carried into the topic Signaling in the Skin: Andrzej Dlugosz (University of Michigan, Ann Arbor) gave an overview of hedgehog signaling with a focus on tumor formation. Xiao-Jing Wang (Oregon Health and Science University, Portland) described how she discovered that SMAD7 had an alternative signaling path that affected wnt signaling by binding to β-catenin. Anthony Oro (Stanford University, Palo Alto, CA) discussed the temporal regulation of hedgehog signaling. Dennis Roop (Baylor College of Medicine, Houston, TX) ended this session with a discussion of the effect of p63 on epidermal development.
      Breakout Sessions. Kurt Stenn, Diane Thiboutot, Andrzej Dlugosz, George Cotsarelis, Dennis Roop, and Howard Chang led discussions of “Translations to New Dermatology Practice.” Emily Fain Epstein from Insight Partners helped facilitate the breakout sessions. The results of these discussions can be found at http://www.montagnasymposium.org/ under “Highlights of Clinician/Scientist Translational Discussion Session from the 55th Annual Montagna Symposium on the Biology of Skin.”
      To end the Symposium, Carl Baker, PhD, Program Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS; National Institutes of Health; Bethesda, MD), discussed new directions at the NIAMS and the potential for funding.
      As in the past, we were able to assist nine young investigators in attending the Symposium through a generous donation by the Eugene M. Farber family to the Society for Investigative Dermatology (SID). The following scientists won the 2006 SID Eugene M. Farber Travel Awards for Young Investigators:
      Kristin Braun, PhD
      Institute of Cell and Molecular Science, Centre for Cutaneous Research, Barts and The London, Queen Mary's School of Medicine and Dentistry, London, UK
      “The cell surface marker MTS24 identifies a novel population of follicular keratinocytes with characteristics of progenitor cells”
      Katherine Fantauzzo, MA
      Department of Genetics and Development, Columbia University, New York, NY
      “Expression of TRPS1 and identification of potential downstream targets during murine hair follicle morphogenesis”
      Elina Järvinen, MSC
      Developmental Biology Research Program, Institute of Biotechnology, University of Helsinki, Finland
      “Increased epithelial β-catenin unlocks renewal of mouse teeth”
      Kim B. Jensen, PhD
      Keratinocyte Laboratory, London Research Institute, Cancer Research UK, London, UK
      “Single cell expression profiling of human epidermal stem and transit amplifying cells: Lrig1 is a regulator of stem cell quiescence”
      Simona Leonardi, PhD
      Biotechnology Unit, Ente per le Nuove Tecnologie, l'Energia e l'Ambiente, Centro Ricerche Casaccia, Rome, Italy
      “Hair-cycle dependent basal cell carcinoma tumorigenesis is strongly influenced by genetic background of irradiated Ptc1+/- mice”
      Andrei N. Mardaryev, MD
      Department of Dermatology, Boston University School of Medicine, Boston, MA
      “Transgenic expression of the BMP antagonist noggin in skin leads to hair follicle-derived tumors and increases epidermal susceptibility to chemical carcinogenesis”
      Michael Rendl, MD
      Laboratory of Mammalian Cell Biology and Development, Howard Hughes Medical Institute, The Rockefeller University, New York, NY
      “Maintenance of dermal papilla identity and hair follicle inductivity”
      Steve H. Yang, BA
      Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI
      “Hedgehog-Wnt interactions in ectopic epithelial bud development”
      Monica Yunta-Gonzalez, PhD
      Departments of Dermatology and Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA
      “WNT/beta-catenin signaling is required for multiple stages of embryonic and postnatal mammary gland development”
      (MSBS Director's Award not funded by SID/Farber Awards)
      Michelle Shih, BA
      Biomedical Sciences Graduate Program, Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA
      “DGAT1 modulates vitamin A homeostasis in the skin”

      ACKNOWLEDGMENTS

      We greatly appreciate the 41 years of support of this conference by the National Institutes of Health and the current support by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR009431). We thank all who gave generously; the Symposium could not continue without the support of foundations, corporations, and people dedicated to advances in dermatology such as the Eugene M. Farber family.