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The role of the transcription factors oct-6 and krox-24 in development of the cells of the schwann cell lineage

Objective



Research objectives and content
The long term aim is to understand the developmental regulation of differentiation in the Schwann cell lineage. In this project, it is proposed to analyse the role of the POU domain transcription factor, Oct 6/Tst-l/SCIP and the zinc finger transcription factor Krox-24 in the development of Schwann cell precursors and their transition to Schwann cells, and to examine the role of Krox-24 in the maturation of non-myelin-forming Schwann cells. The basic plan is to use techniques developed for the study of normal Schwann cell precursors and Schwann cells to determine how the phenotype of these cells is affected in Oct 6 and Krox-24 knockout mice. In order to get this aims we will study: - The Schwann cell precursor survival behavior in the mutants - The antigenic phenotype of mutant cells (NCAM, Ll, p75NGFr, A5E3, Ran-2, vimentin, nestin and GAP-43 expression). - The progression from precursors to Schwann cells (S100 positive, tri- or bipolar cells that can survive in defined medium when cultured at 2()()() cells/coverslip) in DNRG. - The antigenic profile of Schwann cells from EIG/17/lX mutant nerves and their responses to mitogens such as FGF and anrg. - The survival ability of Schwann cells from mutant nerves in low density culture. - The ability of the Oct 6-- to achieve normal 1:1 segregation and myclinate in co-culture with DRG neurons. - The morphology and axon relationships of precursors and non-myelin cells in developing postnatal nerves in Krox-24 -animals. - The differentiation of non-myelin cells in postnatal nerves of Krox-24 -- mice. Training content (objective, benefit and expected impact) My stay in this laboratory, working with an expert and prestigious group, would be a great opportunity in order to be trained in cell culture procedures and both genetic and molecular techniques. This training could complement my experience in Cell Biology. On the other hand, I would have the exceptional opportunity to work with knockout mice. I have been working during the last three months in the lab of the Prof Mirsky and Prof Jessen and I am already integrated into their group and I have obtained some exciting results, so it would be really interesting to me to be able to carry on with this project. I expect to acquire a great experience which allows me to introduce this research line in my region when I come back to Spain.
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UNIVERSITY COLLEGE LONDON
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