Neuronal Transplants as an Organotypic Brain Tumor Model

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DESCRIPTION (provided by applicant): An organotypic model for CNS development and tumors will be established by xenotransplantation of multi-potent neural precursors from adult rats and from postnatal human cadavers into immune-deficient mice. Initial studies on these neural precursors will be carried out in vitro in order to document asymmetric cell division, to determine whether this is associated with asymmetric distribution of cell fates, and to identify the protein determinants of asymmetric cell division. Candidate determinants have been identified based on their homology with determinants identified genetically in Drosophila. Immunocytochemical methods will be used to determine whether these homologs show asymmetric and dynamic distribution during asymmetric division in vitro and in the organotypic model, as expected from the Drosophila model. Candidate determinants include the tumor suppressor Dlg and its binding partner Pins, which were discovered in this laboratory and are the main focus of the parent grant. The results will show whether this organotypic model allows division and development patterns typical of normal CNS, and whether it is a useful system in which to investigate the development of human stem cells and the cellular abnormalities arising in CNS tumors. Eventually it may be possible to use it to explore the effectiveness of therapeutic strategies including gene therapy and drug treatments.