Epithelial bud development is the first step in the formation of lung, limb, teeth and hair. To form a bud from a single layer of epithelium, cells must utilize their cytoskeleton in conjunction with cell-cell and cell-substratum connections to remodel their interactions with neighboring cells. Of major importance in defining cell shape, polarity and migration is the actin cytoskeleton and its associations with E-cadherin-mediated cell-cell junctions (adherens junctions) and b1 integrin-mediated cell substratum junctions (focal adhesions). Precisely how these junctions utilize actin filaments to accomplish this remodeling is unknown. However, when the process of epithelial bud formation goes astray, disastrous results can include not only malformation of physical structures but also malignancies. Mice will be used as a source of cultured epithelial stem cells and their skin used as models to characterize the Wnt and noggin mediated changes in a) actin dynamics, cell adhesion and migration, and b) gene transcription, at the early stages of hair follicle bud development. The long-term goal is to understand how various signaling pathways converge to regulate follicular morphogenesis and how misregulation leads to cancer.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AR050340-03
Application #
6898348
Study Section
Special Emphasis Panel (ZRG1-F05 (20))
Program Officer
Tyree, Bernadette
Project Start
2003-07-01
Project End
2006-06-30
Budget Start
2005-07-01
Budget End
2006-06-30
Support Year
3
Fiscal Year
2005
Total Cost
$48,928
Indirect Cost
Name
Rockefeller University
Department
Biology
Type
Other Domestic Higher Education
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065
Lowry, William E; Blanpain, Cedric; Nowak, Jonathan A et al. (2005) Defining the impact of beta-catenin/Tcf transactivation on epithelial stem cells. Genes Dev 19:1596-611