Remarkable phenotypic plasticity of epithelial cells underlies developmental morphogenesis, epithelial repair and tumor invasiveness. Driving all these behaviors are changes in cell adhesion and the cytoskeleton, and understanding their regulatory pathways in vivo may lead to better diagnosis and treatment of birth defects and cancer. The evolutionarily conserved family of formin proteins have emerged as important cytoskeleton effectors downstream of Rho GTPases. In vitro, they are involved in cytokinesis, cell elongation and migration, and in formation of cell-cell adhesions. However, their function in the context of a whole tissue during morphogenesis has not been explored. The host laboratory established epidermal morphogenesis of the C. elegans embryo as an excellent model for epithelial morphogenesis, in which it is possible to combine powerful genetic and genomic tools with clear imaging of the cytoskeleton at the single cell level. My goal is to find which C. elegans formins play a role in epidermal morphogenesis and elucidate their function in regulating cell-cell adhesion and the cytoskeleton. This will be accomplished through a combination of genetics, 4D microscopy and RNAi. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM078747-03
Application #
7489833
Study Section
Special Emphasis Panel (ZRG1-F05-J (20))
Program Officer
Flicker, Paula F
Project Start
2006-09-07
Project End
2009-09-06
Budget Start
2008-09-07
Budget End
2009-09-06
Support Year
3
Fiscal Year
2008
Total Cost
$48,796
Indirect Cost
Name
University of Wisconsin Madison
Department
Zoology
Type
Schools of Arts and Sciences
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Neukomm, Lukas J; Frei, Andreas P; Cabello, Juan et al. (2011) Loss of the RhoGAP SRGP-1 promotes the clearance of dead and injured cells in Caenorhabditis elegans. Nat Cell Biol 13:79-86
Zaidel-Bar, Ronen; Geiger, Benjamin (2010) The switchable integrin adhesome. J Cell Sci 123:1385-8
Zaidel-Bar, Ronen; Joyce, Michael J; Lynch, Allison M et al. (2010) The F-BAR domain of SRGP-1 facilitates cell-cell adhesion during C. elegans morphogenesis. J Cell Biol 191:761-9
Zaidel-Bar, Ronen; Miller, Shahar; Kaminsky, Rachel et al. (2010) Molting-specific downregulation of C. elegans body-wall muscle attachment sites: the role of RNF-5 E3 ligase. Biochem Biophys Res Commun 395:509-14
Zaidel-Bar, Ronen (2009) Evolution of complexity in the integrin adhesome. J Cell Biol 186:317-21
Lockwood, Christina; Zaidel-Bar, Ronen; Hardin, Jeff (2008) The C. elegans zonula occludens ortholog cooperates with the cadherin complex to recruit actin during morphogenesis. Curr Biol 18:1333-7