The long-term objective of this laboratory is to understand the molecular basis of epithelial appendage morphogenesis. Epithelial appendages including hair, nail, feather, teeth, etc. are integral parts of the integument. Diseases and injuries involving these appendages can be detrimental to the survival of the animal. However, research on the development and regeneration of epithelial appendages has lacked. We hope this research will form the basis to promote novel approaches and ideas to manage pathological conditions involving epithelial appendages. We use the chicken feather as an experimental model. In the last funding period, we studied the roles of adhesion molecules and searched for their regulators. We found heterogenous molecular distribution in the epithelial placode develop from an initially homogeneous feather primordia. Molecules like Sonic hedgehog and FGF4 are radically symmetrically distributed, while others become anterior-posterior asymmetrically compartmentalized, with BMP2, 4 and Msx1, 2 in the anterior side, Serrate 1, Wnt7a, BrdU labeling in the posterior side, and Notch 1 forming a mid-stripe. Preliminary perturbation of the molecular balance arrested placode outgrowth in different ways. We hypothesize that the interactions between the anterior and posterior compartments are essential for the generation of a continuous growth zone required to drive the formation of the proximal-distal axis. This growth zone later becomes the feather collar (=hair matrix). Failure to form the growth zone leads to limited growth as seen in scale, but can be rescued to form feather buds by retinoic acid which may induce an ectopic compartment. This process is analogous to the formation of Drosophila appendages from epithelial imaginal discs and the limb bud apical ectodermal ridge, resulting from interactions between dorsal and ventral compartment signals. To test the hypothesis, we will use in situ, BrdU labeling and DiI labeling to establish molecular expression pattern and cell behavior. Differences among scales, feathers and feathery scales will be compared. For molecular candidates, we will focus on Notch and Wnt 7a pathways, and their interactions with other molecules. Retroviral gene transduction together with embryology techniques will be used to generate several experimental conditions including gene over-expression, dominant negative receptors, virus susceptible/resistant chimeric explants, and juxtaposition of anterior/posterior domains. Results and techniques developed here will advance our understanding in epithelial appendage morphogenesis and contribute to the development of gene therapy on hair matrix cells or dissociated keratinocytes for the regeneration of fully functional skin.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR042177-06
Application #
6137318
Study Section
General Medicine A Subcommittee 2 (GMA)
Program Officer
Moshell, Alan N
Project Start
1995-01-01
Project End
2003-12-31
Budget Start
2000-01-01
Budget End
2000-12-31
Support Year
6
Fiscal Year
2000
Total Cost
$312,921
Indirect Cost
Name
University of Southern California
Department
Pathology
Type
Schools of Medicine
DUNS #
041544081
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
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 :
Hughes, Michael W; Jiang, Ting-Xin; Plikus, Maksim V et al. (2018) Msx2 Supports Epidermal Competency during Wound-Induced Hair Follicle Neogenesis. J Invest Dermatol 138:2041-2050
Lei, Mingxing; Schumacher, Linus J; Lai, Yung-Chih et al. (2017) Self-organization process in newborn skin organoid formation inspires strategy to restore hair regeneration of adult cells. Proc Natl Acad Sci U S A 114:E7101-E7110
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
Lei, Mingxing; Chuong, Cheng-Ming (2016) STEM CELLS. Aging, alopecia, and stem cells. Science 351:559-60
Huang, Chin-Fu; Chang, Ya-Ju; Hsueh, Yuan-Yu et al. (2016) Assembling Composite Dermal Papilla Spheres with Adipose-derived Stem Cells to Enhance Hair Follicle Induction. Sci Rep 6:26436
O'Connor, J K; Zheng, X-T; Sullivan, C et al. (2015) Evolution and functional significance of derived sternal ossification patterns in ornithothoracine birds. J Evol Biol 28:1550-67
Lei, Mingxing; Lai, Xiangdong; Bai, Xiufeng et al. (2015) Prolonged overexpression of Wnt10b induces epidermal keratinocyte transformation through activating EGF pathway. Histochem Cell Biol 144:209-21

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