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 led 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 beta-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. ? ? ?
