The goal of this research proposal is to understand the role of various endocytic trafficking events in the regulation of Notch and Wingless signaling. Focusing on the Drosophila wing, where the pathways interact, I have performed preliminary studies using Hrs, a protein implicated in multivesicular body formation. I have found genetic interactions with signaling members, as well as changes in protein levels and localization, suggestive of a role in signal regulation. Here, I plan to tease apart endocytosis by analyzing the importance of each step of trafficking on Notch and Wingless signaling regulation. I will perform a detailed study of the subcellular localization of signaling members by microscopy. Then, using genetic tools that modulate vesicle trafficking events, I will characterize changes in protein subcellular localization and analyze the resultant wing phenotypes. Finally, I will investigate the role of endocytosis in establishing the Wingless morphogen gradient. Together, these studies will contribute to our understanding of Notch and Wingless signaling and provide insight into how these pathways control cell proliferation and cell fate determination.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30ES011725-04
Application #
6861011
Study Section
Special Emphasis Panel (ZRG1-F05 (20))
Program Officer
Humble, Michael C
Project Start
2002-03-01
Project End
2006-02-24
Budget Start
2005-03-01
Budget End
2006-02-24
Support Year
4
Fiscal Year
2005
Total Cost
$23,440
Indirect Cost
Name
Baylor College of Medicine
Department
Genetics
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
Seto, Elaine S; Bellen, Hugo J (2006) Internalization is required for proper Wingless signaling in Drosophila melanogaster. J Cell Biol 173:95-106