To understand morphogenesis, one must know how the actin cytoskeleton forms and how it is taken apart. Presently there is little known about how this occurs in a developing animal and less still in a developing eye. Our goal is to bring light to this area of eye research, increasing our ability to visualize how the actin cytoskeleton is regulated during the morphogenesis of the eye. We will take a genetic approach, using Drosophila meIanogaster as a model system. We have been studying the twinstar (tsr) gene, which is the Drosophila homologue of cofilin, a protein which has a major role in reorganizing the actin cytoskeleton. We have shown that tsr is required for cell motility during ovary development. We have also been able to show that tsr is required during the morphogenesis of the retina by using a genetic technique that we developed called repressor sensitive (RS) mutation. With a tsr RS mutation, we can specifically repress the expression of tsr during late stages of eye development, allowing us to study the role of tsr at this stage without concern for tsr's affects in other tissues or other times of development. Our results suggest that tsr is required for the proper development of the rhabdomere and also for retinal elongation. We now propose to continue the analysis of the role of tsr during eye morphogenesis, and use the RS mutation technique to study the role of other actin cytoskeleton regulatory genes during eye morphogenesis, including the Drosophila homologues of LIM kinase, actin interacting protein 1 (Aip 1), PAK, rac and the Arp2/3 complex. We will also screen for novel genes that genetically interact with tsr during late stages of eye morphogenesis. Our results will significantly add to our knowledge of how structures required for vision are formed by modification of the actin cytoskeleton.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY014876-04
Application #
7090605
Study Section
Special Emphasis Panel (ZRG1-VISC (01))
Program Officer
Mariani, Andrew P
Project Start
2003-08-01
Project End
2007-06-30
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
4
Fiscal Year
2006
Total Cost
$366,749
Indirect Cost
Name
University of California Los Angeles
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095