This proposal is from an established investigator who has published excellent work in this field. He seeks to continue to characterize the interactions between the mesoderm and the extracellular matrix as it forms in early Xenopus embryos. As mesoderm cells form in the embryo, they become motile, and by a complex and ill-understood mechanism, move inside the embryo. As they do so, they behave differently according to whether they will form dorsal, ventral, anterior or posterior structures. One of the substrata of the ingressing mesoderm is the extracellular matrix secreted by the cells of the blastocoel roof. It is the interaction between mesoderm cells and the extracellular matrix glycoprotein that is the subject of this proposal.
The aims are 1) to establish the roles of cell-matrix interactions during gastrulation using function-blocking reagents, 2) To develop """"""""reporters"""""""" of sites of integrin activation that will be used to monitor stage and region-specific changes in receptor activation, and 3) to see if patterns of mesodermal gene expression require cell-ecm interaction.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD026402-12
Application #
6387565
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Program Officer
Klein, Steven
Project Start
1990-01-01
Project End
2003-07-31
Budget Start
2001-08-01
Budget End
2002-07-31
Support Year
12
Fiscal Year
2001
Total Cost
$298,247
Indirect Cost
Name
University of Virginia
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Rozario, Tania; Mead, Paul E; DeSimone, Douglas W (2014) Diverse functions of kindlin/fermitin proteins during embryonic development in Xenopus laevis. Mech Dev 133:203-17
Bjerke, Maureen A; Dzamba, Bette J; Wang, Chong et al. (2014) FAK is required for tension-dependent organization of collective cell movements in Xenopus mesendoderm. Dev Biol 394:340-56
DeSimone, Douglas W; Horwitz, A Rick (2014) Cell Biology. Many modes of motility. Science 345:1002-3
Weber, Gregory F; Bjerke, Maureen A; DeSimone, Douglas W (2012) A mechanoresponsive cadherin-keratin complex directs polarized protrusive behavior and collective cell migration. Dev Cell 22:104-15
Wei, Shuo; Xu, Guofeng; Bridges, Lance C et al. (2012) Roles of ADAM13-regulated Wnt activity in early Xenopus eye development. Dev Biol 363:147-54
Schwarzbauer, Jean E; DeSimone, Douglas W (2011) Fibronectins, their fibrillogenesis, and in vivo functions. Cold Spring Harb Perspect Biol 3:
Weber, Gregory F; Bjerke, Maureen A; DeSimone, Douglas W (2011) Integrins and cadherins join forces to form adhesive networks. J Cell Sci 124:1183-93
Wei, Shuo; Xu, Guofeng; Bridges, Lance C et al. (2010) ADAM13 induces cranial neural crest by cleaving class B Ephrins and regulating Wnt signaling. Dev Cell 19:345-52
Wei, Shuo; Whittaker, Charles A; Xu, Guofeng et al. (2010) Conservation and divergence of ADAM family proteins in the Xenopus genome. BMC Evol Biol 10:211
Rozario, Tania; DeSimone, Douglas W (2010) The extracellular matrix in development and morphogenesis: a dynamic view. Dev Biol 341:126-40

Showing the most recent 10 out of 56 publications