Experiments in this proposal are designed to determine if Rho proteins regulate morphogenic movements during Xenopus gastrulation. The preliminary results presented suggest that RhoA regulates a specific cell movement which occurs during gastrulation, convergent-extension movements. Experiments proposed in Specific Aim number 1 will further investigate this possibility by determining if convergent-extension movements of endogenous mesoderm in vitro require Rho protein function. Experiments in Specific Aim number 2 will determine if Rho kinases, which links RhoA to regulation of the actin cytoskeleton, mediate convergent-extension movements during gastrulation. Finally, experiments in Specific Aim number 3 are design to isolate Xenopus RhoA homologues and determine if they mediate convergent-extension movements during gastrulation. These experiments are important to human health because of the role that Rho proteins play in cell movements in human disease. Rho proteins and Rho kinase have been shown to play a pivotal role in tumor formation, metatasis and in hypertension. Therefore, a study of the in vivo role of these molecules during development may provide further clues as to how their activity may be regulated in these diseases.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32HD008605-02
Application #
6363375
Study Section
Cell Development and Function Integrated Review Group (CDF)
Program Officer
Klein, Steven
Project Start
2001-03-01
Project End
Budget Start
2001-03-01
Budget End
2001-03-31
Support Year
2
Fiscal Year
2001
Total Cost
$2,961
Indirect Cost
Name
Rockefeller University
Department
Anatomy/Cell Biology
Type
Other Domestic Higher Education
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065
Zohn, Irene E; De Domenico, Ivana; Pollock, Andrew et al. (2007) The flatiron mutation in mouse ferroportin acts as a dominant negative to cause ferroportin disease. Blood 109:4174-80
Zohn, Irene E; Anderson, Kathryn V; Niswander, Lee (2007) The Hectd1 ubiquitin ligase is required for development of the head mesenchyme and neural tube closure. Dev Biol 306:208-21
Zohn, Irene E; Li, Yingqiu; Skolnik, Edward Y et al. (2006) p38 and a p38-interacting protein are critical for downregulation of E-cadherin during mouse gastrulation. Cell 125:957-69