The long term objective is to understand the molecular mechanism of how sex hormones differentially regulate the morphogenetic process of organ formation, so that the same primordia, or stem cells, can be molded into distinct phenotypes, forming the basis of sexual dimorphism. Skin appendages are very responsive to hormonal stimulation which lead to sexual dimorphisms. These are frequently observed on the skin surface as changes in the size, shape, color and function of skin appendages. These effects are hormone dependent and region specific as androgen can cause regression of scalp hairs, but stimulate the growth of beards. At times, errors in hormone dependent growth can lead to congenital anomalies and tumors in the prostate, breast or ovary. The normal and abnormal molecular mechanisms of these processes are mostly unknown. Therefore, a good animal model for in vivo and in vitro studies is needed. In mouse hairs, sexual dimorphism is not apparent. We propose to develop a novel model: the growth of tail feathers in roosters and hens, because it is an in vivo physiological process and accessible for analyses. Our previous work suggested that feather growth depends on localized growth zone (LoGZ) activity in the proximal follicle and this activity is regulated by the Wnt/p-catenin pathway. Furthermore we showed that (3-catenin physically associates with the androgen receptor. Here we hypothesize that the differences of male and female tail feathers are due to differences in LoGZ activities and developmental fates as modulated by sex hormones.
Aim 1 will characterize localized hormones, receptors, and enzymes involved in hormone metabolism and identify possible molecular and cellular targets mediating these differences.
Aim 2 will study the cross talk between sex hormones and growth related pathways and test whether they are mediated by the canonical 3-catenin pathway. We will explore interactions of sex hormone receptors with members of the Wnt/p-catenin pathway and other co- activators and co-repressors that may modulate the differences of organ formation and growth between hormone responsive and non-responsive regions and between male and female feathers. This novel model is likely to yield new understanding to the molecular nature underlying how sex hormones regulate growth control in various organs and tissues.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
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Special Emphasis Panel (ZRG1-MOSS-K (06))
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Baker, Carl
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University of Southern California
Schools of Medicine
Los Angeles
United States
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Lin, Chih-Min; Jiang, Ting Xin; Baker, Ruth E et al. (2009) Spots and stripes: pleomorphic patterning of stem cells via p-ERK-dependent cell chemotaxis shown by feather morphogenesis and mathematical simulation. Dev Biol 334:369-82
Mayer, Julie Ann; Foley, John; De La Cruz, Damon et al. (2008) Conversion of the nipple to hair-bearing epithelia by lowering bone morphogenetic protein pathway activity at the dermal-epidermal interface. Am J Pathol 173:1339-48
Widelitz, Randall B; Veltmaat, Jacqueline M; Mayer, Julie Ann et al. (2007) Mammary glands and feathers: comparing two skin appendages which help define novel classes during vertebrate evolution. Semin Cell Dev Biol 18:255-66
Widelitz, Randall B; Baker, Ruth E; Plikus, Maksim et al. (2006) Distinct mechanisms underlie pattern formation in the skin and skin appendages. Birth Defects Res C Embryo Today 78:280-91
Lin, Chih-Min; Jiang, Ting Xin; Widelitz, Randall B et al. (2006) Molecular signaling in feather morphogenesis. Curr Opin Cell Biol 18:730-41