Cell polarity or asymmetry is a universal feature of animal cells that is fundamental to the development and morphogenesis of all organisms. For developmental biologists the recognition that determinants prelocalized within the oocyte act to control axial polarities and cell fates within the embryo has focused great interest on the identity of those determinants and the mechanism of their localization. The unidirectional movements of the microtubule-associated motors, dyneins, and kinesins, provide an important mechanism for the positioning of cellular organelles and molecules. This mechanism may underlie the polarized transport and targeting of morphogenetic determinants within oocytes and embryos. The proposed research will test this hypothesis. Our previous analysis of recessive lethal dynein mutations has indicated that dynein function is required during oogenesis. Moreover, an aymmetric accumulation of the dynein motor to, and within, the oocyte is disrupted by mutations in genes that are required for oocyte specification and differentiation. Our planned experiments will (1) characterize the cytological and molecular phenotypes of oocytes that are mutant for dynein function, (2) test the hypothesis that cytoskeletal polarity is an underlying component of oocyte asymmetry which accounts for dynein accumulation and localization within the oocyte, and (3) to extend our genetic and molecular analyses of the pathways for cytoskeletal transport in oogenesis. Overall, these studies are designed to enhance understanding of the roles of motor proteins in the specification of embryonic axes in the fly egg chamber in articular and the generation of cell olarity in general.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM053695-04
Application #
6019124
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1996-09-01
Project End
2002-08-31
Budget Start
1999-09-01
Budget End
2002-08-31
Support Year
4
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Genetics
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Boylan, Kristin L M; Mische, Sarah; Li, Mingang et al. (2008) Motility screen identifies Drosophila IGF-II mRNA-binding protein--zipcode-binding protein acting in oogenesis and synaptogenesis. PLoS Genet 4:e36
Siller, Karsten H; Serr, Madeline; Steward, Ruth et al. (2005) Live imaging of Drosophila brain neuroblasts reveals a role for Lis1/dynactin in spindle assembly and mitotic checkpoint control. Mol Biol Cell 16:5127-40
Papoulas, Ophelia; Hays, Thomas S; Sisson, John C (2005) The golgin Lava lamp mediates dynein-based Golgi movements during Drosophila cellularization. Nat Cell Biol 7:612-8
Wang, Lei; Hare, Michael; Hays, Thomas S et al. (2004) Dynein light chain LC8 promotes assembly of the coiled-coil domain of swallow protein. Biochemistry 43:4611-20
Silvanovich, Andre; Li, Min-Gang; Serr, Madeline et al. (2003) The third P-loop domain in cytoplasmic dynein heavy chain is essential for dynein motor function and ATP-sensitive microtubule binding. Mol Biol Cell 14:1355-65
Boylan, K; Serr, M; Hays, T (2000) A molecular genetic analysis of the interaction between the cytoplasmic dynein intermediate chain and the glued (dynactin) complex. Mol Biol Cell 11:3791-803