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Projekt
Functional analysis of Notch1 in the maintenance and differentiation of adult mamammalian neural stem cells.
Antragsteller
Professor Dr. Verdon Taylor, Ph.D.
Fachliche Zuordnung
Kinder- und Jugendmedizin
Förderung
Förderung von 2003 bis 2008
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 5403163
Diseases and injuries affecting the integrity of the vertebrate brain are particularly debilitating. It was long thougth that inept regeneration of the mammalian adult central nervous system was due to a lack of multipotent, self-replicating cells or "stem cells". Over the last decade evidence has accumulated for the presence of neural stem cells in the postnatal mammalian brain. However, their identity and the mechanisms regulating their differentiation are unclear. We have previously shown that the receptor Notch1 is a central player in maintaining neural stem cell fate in the embryonic neural tube. More recently we demonstrated that Notch1 is expressed by, and functionally activated in clusters of cells within the neurogenic regions of the adult mouse brain. We propose that these Notch1 expressing cells are the elusive neural stem cells. We will address the function of Notch1 in the maintenance and differentiation of adult neural stem cells by conditional gene ablation. We will isolate stem cells from the adult mouse brain and inactivate the Notch1 gene in a controlled and cell-specific manner using the Cre-recombinase system. The effects of Notch1 ablation on adult neural stem cell self-replication, cell fate determination and differentiation will be addressed. We will perform microarray analysis of gene expression to examine molecular pathways controlled by Notch1 in neural stem cells. The combination of gene ablation and microarray technology will greatly facilitate our understanding of the mechanisms controlling neural stem cell differentiation and potentially define new targets for therapeutic intervention.
DFG-Verfahren
Schwerpunktprogramme
