Objective
Our evidence indicates that the paired box genes (pax) function as sequence-specific transcription factors. The paired box genes control the process of embryonic segmentation in Drosophila; accumulating evidence indicates that they control the mammalian development as well. Our goal is to dissect the molecular mechanisms of pax function and to investigate their involvement in particular human diseases such as thyroid cancer, Wilms' tumors, Waardenburg syndrome cases bearing skeletal muscular atrophies (type III) and neuroblastomas. Three human genes of the pax gene family will be investigated in this respect- PAX2, PAX7 and PAX8. PAX8 is expressed in the induced, intensively differentiating parts of the embryonic kidney and thyroid. PAX2 is highly homologous to PAX8 and is also expressed during kidney development. PAX8 and PAX2 may be involved in the genesis of Wilms' tumors that originate in the human embryonic kidney. our studies indicate that these genes are overexpressed in all investigated WTs. Murine Pax7 is expressed in skeletal muscle cells and its human homolog is possibly involved in particular Waardenburg syndrome cases (type III). Extending our already existing project we have chosen four additional approaches to achieve our goal. The entire human PAX2 gene will be cloned and caracterized. We will analyze the alternatively spliced PAX2 transcripts using RT-PCR. In addition the PAX2 cDNA clones isolated from the human kidney and brain cDNA libraries will be sequenced giving us additional information about PAX2 isoforms. The PAX2 gene will be cloned in cosmids and YACs and its exon/intron boundaries will be determined. We will investigate the PAX2 and PAX8 expression in WTs extending our studies on WTs of Russian origin. We will elucidate the cis-acting sequences which govern the kidney- and thyroid-specific expression of the human PAX8 gene as an approach to understand the molecular mechanisms of the embryonic induction. To this end we have already isolated upstream genomic PAX8 sequences which will be tested in transgenic mice. We will clone and characterize the entire human PAX7 gene. Alterations in either the structure or the expression of the PAX7 gene in WSIII cases will be investigated. We will investigate the expression of the human PAX3 and PAX7 genes during normal development and in pathology.
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
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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.
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Funding Scheme
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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
48149 Münster
Germany
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.