: The regulation of organ size is a fundamental mechanism in development. The skin appendage is the best model to study size regulation because of the large number of appendages and the extensive size variation found within one individual organism. Many clinical conditions such as alopecia, hirsutism and even cancer are basically problems of size. The chicken feather is an excellent model because of the large spectrum of graded feather sizes on one individual and the possible variations in special breeds. We hypothesize that the size of feathers is determined through multiple stages of epithelial-mesenchymal interactions, from initiation to growth to resting phases, each modulated by combinatorial positive and negative molecular regulators. We will do molecular mapping of different phases of feather follicles with in situ hybridization and immuno-staining. Preliminary data showed the presence of members of major signaling pathways (e.g. SHH, BMP, Wnt) in different regions of the follicle. We also have identified a novel feather follicle bulge zone that shows long term BrdU label retention that may contain feather stem cells. To search for cellular determinants of feather size, we will engineer chimeric feather follicles made with components from different-sized follicles. To identify molecular determinants, we have developed a feather plucking/regeneration model and can introduce genes to the regenerating feathers using gene therapy technology. Candidate molecules will be chosen by comparative molecular mapping of different-sized follicles, and library subtraction. Preliminary data suggest that the SHH pathway is one of the positive regulators and the BMP pathway is one of the negative regulators for feather size. Alterations of cell proliferation, differentiation (judged by keratin markers) and other signaling molecules will be analyzed to identify crosstalk among molecular pathways. This work will lead to a new understanding of the molecular basis of the size regulation of skin appendages.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR047364-03
Application #
6751249
Study Section
General Medicine A Subcommittee 2 (GMA)
Program Officer
Moshell, Alan N
Project Start
2002-05-01
Project End
2007-04-30
Budget Start
2004-05-01
Budget End
2005-04-30
Support Year
3
Fiscal Year
2004
Total Cost
$315,250
Indirect Cost
Name
University of Southern California
Department
Pathology
Type
Schools of Medicine
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Wu, Ping; Yan, Jie; Lai, Yung-Chih et al. (2018) Multiple Regulatory Modules Are Required for Scale-to-Feather Conversion. Mol Biol Evol 35:417-430
Lai, Yung-Chih; Liang, Ya-Chen; Jiang, Ting-Xin et al. (2018) Transcriptome analyses of reprogrammed feather / scale chimeric explants revealed co-expressed epithelial gene networks during organ specification. BMC Genomics 19:780
Qiu, Weiming; Chuong, Cheng-Ming; Lei, Mingxing (2018) Regulation of melanocyte stem cells in the pigmentation of skin and its appendages: Biological patterning and therapeutic potentials. Exp Dermatol :
Widelitz, Randall B; Lin, Gee-Way; Lai, Yung-Chih et al. (2018) Morpho-regulation in diverse chicken feather formation: Integrating branching modules and sex hormone-dependent morpho-regulatory modules. Dev Growth Differ :
Wu, Ping; Lai, Yung-Chih; Widelitz, Randall et al. (2018) Comprehensive molecular and cellular studies suggest avian scutate scales are secondarily derived from feathers, and more distant from reptilian scales. Sci Rep 8:16766
Wang, Shuo; Stiegler, Josef; Wu, Ping et al. (2017) Heterochronic truncation of odontogenesis in theropod dinosaurs provides insight into the macroevolution of avian beaks. Proc Natl Acad Sci U S A 114:10930-10935
Cooke, Thomas F; Fischer, Curt R; Wu, Ping et al. (2017) Genetic Mapping and Biochemical Basis of Yellow Feather Pigmentation in Budgerigars. Cell 171:427-439.e21
Li, Ang; Figueroa, Seth; Jiang, Ting-Xin et al. (2017) Diverse feather shape evolution enabled by coupling anisotropic signalling modules with self-organizing branching programme. Nat Commun 8:ncomms14139
Cho, Jung-Hwa; Swanson, Carter J; Chen, Jeannie et al. (2017) The GCaMP-R Family of Genetically Encoded Ratiometric Calcium Indicators. ACS Chem Biol 12:1066-1074
Lai, Yung Chih; Chuong, Cheng-Ming (2016) The ""tao"" of integuments. Science 354:1533-1534

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