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Genetic control of neuron-glial fate switching in the embryonic neural tube

Ziel

Oligodendrocyte cells are myelin-forming cells of the central nervous system and are involved in many demyelinating diseases such as multiple sclerosis. Understanding how oligodendrocytes are generated from immature precursors cells in the embryo is of increasing importance for potential therapeutic applications. The aim of the proposal is to investigate the genetic control of oligodendrocyte specification. We propose:
1 ) to examine PAX6 and NKX2.2 mutant mice to see whether these transcription factors control oligogenic OLIG1/2and SOX10 gene expression.
2) to fully characterize oligogenic genes that Pr Richardson's team has previously isolated by a subtractive screen from chick spinal cord. We plan to isolate full-length cDNA clones, then to do a full characterization and lastly to isolate full-length mouse genomic clones and map these in order to construct targeting vector for knockout experiments in mice.
3) to search for more oligogenic genes by micro-dissecting the ventricular zone of mouse spinal cord at different ages, using the laser capture microscope (LCM), followed by micro-scale cDNA library construction and screening.

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