Objective
The Wilms tumour suppressor, Wt1 is a transcription factor of the zinc-finger type. Evidence supports the hypothesis that Wt1 is important for Epithelial Mesenchymal Transition (EMT) in epicardial cells during cardiac development. Wt1 may be playing a key role in maintaining the balance of proliferation versus differentiation of cardiac vascular progenitor cells derived from the epicardium. Further evidence implicates Wt1 in the vascular regenerative response to myocardial ischaemia.
The proposed project explores these hypotheses and attempts to dissect the mechanisms involved. In order to test the hypotheses about Wt1 function in this pathway we will inactivate Wt1 at different stages during the progression from proepicardium, to epicardium to Epicardial derived cells (EPDCs), to vascular tissue. I will make the appropriate crosses to produce mice that carry a floxed Wt1 allele opposite the Wt1 GFP allele and also carrying the tamoxifen-inducible Cre. Thus it should be possible to examine the influence of Wt1 disruption on the development of the principal known Wt1 targets in cardiovascular system.
In addition, I will determine whether they may be contributing to the observed cardiac defect observed in the Wt1 null mice. Culturing epicardial explants from these mice I will directly demonstrate the importance of this factor in the EMT transformation during heart formation. I will also identify the molecular mechanism of Wt1 induced EMT and maintaining of cardiac vascular progenitor cells. Using chromatin immunoprecipitation I will investigate the hypothesis that Wt1 activates the Snail gene and that defects in the EMT and EPDCs proliferation may result from reduced Snail production in the Wt1 null mice. In addition, I will also analyse if over-expression of Sn ail in epicardial cells could revert the Wt1 null phenotype. Finally, using the conditional Wt1 line I will be able to test whether Wt1 function is important for the vascular repair response to ischaemia
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences medical biotechnology cells technologies stem cells
- medical and health sciences clinical medicine oncology
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP6-2005-MOBILITY-5
See other projects for this call
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
LONDON
United Kingdom
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.