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Color variation is one of the most readily apparent differences among closely related animals, and has been studied extensively as a model for Mendelian genetics over the last 100 years. Our laboratory is interested in the mechanisms that give rise to eye, hair, and skin coloration, both as a tool for studying gene action and interaction, and because many signaling pathways used by the pigmentary system play important roles in human development and disease.All mammals use the same genetic toolbox, and several mouse coat color mutations have human counterparts such as oculocutaneous albinism or Chediak-Higashi syndrome. Applying the genetics of mouse hair color as a model, however, is relevant not only to rare inborn errors but also to common diseases including diabetes and obesity, neurodegeneration, and skin cancer. Production of normal hair and skin color depends on a series of processes--cell migration, stem cell renewal, paracrine regulation of cell physiology--used in many different contexts throughout the body; pigmentation phenotypes are especially well-suited for studying these processes because mutations are efficiently recognized, subtle effects on gene expression are easily detected, and the cell types and tissues involved are amenable to experimental manipulation.Our original interest in mouse coat color genetics stems from mutations that cause a back-and-forth switch between pigment granules characteristic of red hair, to those characteristic of black, brown, or blond hair. Studies of these pigment type-switching mutations have identified one set of pathways important for body weight regulation, and another set of pathways implicated in neurodegeneration. Several current projects in the laboratory are directed at specific aspects of these pathways.