Asymmetric cell division is a general mechanism of achieving cellular diversity in metazoans and therefore vital to our long-term understanding of development and genetic disease. The somatic gonadal precursors (SGPs) of C. elegans undergo asymmetric cell division, establishing the proximal-distal axis of the gonad. As a result of this asymmetric division, POP-1/TCF is differentially localized in the SGP daughters. The Wnt pathway regulates POP-1 localization, as does components of the cell cycle machinery and the TRA-1/GLI transcription factor. However, the mechanism by which these regulators control POP-1 asymmetry is unknown. The broad goal of this proposal is to understand the molecular mechanisms of how asymmetric cell division is regulated, using the gonad of C. elegans as a model. To this end, the mechanism underlying the control of the Wnt pathway on the asymmetric localization of POP-1 in the SGPs will be determined. A potential role of cell-cell contact in regulating the Wnt pathway will be examined. Finally, use of both forward and reverse genetics methods available in C. elegans will identify new genes that function in asymmetric division, including potential targets of TRA-1/GLI and the cell cycle machinery.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM075598-02
Application #
7133002
Study Section
Special Emphasis Panel (ZRG1-F05 (20))
Program Officer
Dearolf, Charles R
Project Start
2006-03-01
Project End
2009-02-28
Budget Start
2007-03-01
Budget End
2008-02-29
Support Year
2
Fiscal Year
2007
Total Cost
$48,796
Indirect Cost
Name
University of Wisconsin Madison
Department
Biochemistry
Type
Schools of Earth Sciences/Natur
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Phillips, Bryan T; Kimble, Judith (2009) A new look at TCF and beta-catenin through the lens of a divergent C. elegans Wnt pathway. Dev Cell 17:27-34
Chesney, Michael A; Lam, Ngan; Morgan, Dyan E et al. (2009) C. elegans HLH-2/E/Daughterless controls key regulatory cells during gonadogenesis. Dev Biol 331:14-25
Liu, Jing; Phillips, Bryan T; Amaya, Maria F et al. (2008) The C. elegans SYS-1 protein is a bona fide beta-catenin. Dev Cell 14:751-61
Phillips, Bryan T; Kidd 3rd, Ambrose R; King, Ryan et al. (2007) Reciprocal asymmetry of SYS-1/beta-catenin and POP-1/TCF controls asymmetric divisions in Caenorhabditis elegans. Proc Natl Acad Sci U S A 104:3231-6