Tenascin-C and neural stem cell differentiation

• Applicant: Privatdozent Dr. Alexander von Holst
• Subject Area: Pediatric and Adolescent Medicine
• Term: from 2002 to 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5377755

The project proposes to analyse the effects of the extracellular matrix molecule tenascin-C on neural stem cells and its localization in vivo with respect to the neural stem niche. Initial observations argue for a role of tenascin-C in the control of progenitor cell proliferation within the oligodendrocyte lineage. Here, the influence of tenascin-C on proliferation, differentiation, cell fate and self-renewal of neural stem cells will be examined and quantified using neurosphere cultures as an established model system for neural stem cells. The effects of tenascin-C will be attributed to defined domains through the use of fusionproteins representing specific tenascin-C fragments. Such functionally characterized domains should selectively activate their cognate receptors, which will be identified through a candidate approach for known tenascin-C receptors or, alternatively, by systematic screening procedures. In addition, an induction gene trap procedure will be applied to identify potential target genes of tenascin-C. The validation of tenascin-C receptors and potential target genes requires a thorough expression analysis and precise colocalization in wildtype animals. Furthermore, target genes should be misregulated in tenascin-C deficient mice in vivo. In parallel, neurosphere cultures derived from these animals will be compared to wildtype cultures and analysed for molecular and cellular alterations. Furthermore, target genes can be validated in such cultures, were they should be able to rescue defects after transfection, if they are part of the signaltransduction machinery used by tenascin-C.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1109: Embryonal and Tissue-Specific Stem Cells - Regenerative Systems for Cell and Tissue Repair
• Participating Person: Professor Dr. Andreas Faissner