Neurale Stammzellen des adulten Gehirns: Transdifferenzierung und Rekrutierung ependymaler und endothelialer Zellen

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There is accummulating evidence that neural stem cells exist in the adult mammalian brain. To date, at least three "neurogenic regions" habe been identified, namely the subventricular zone, the hippocampus and the olfactory bulb. Our previous observations suggest that the angiogenesis factor vascular endothelial growth factor (VEGF), previously thought to act almost exclusively on the cardiovascular system, is a regulator of adult stem cell activity and neurogenesis. To specifically test this hypothesis, we plan to make use of genetic mouse models with conditional inactivation of the VEGF gene. We plan to use VEGF lox/lox-GFAPcre mice which-due to the specific activity of crerecombinase-do not express VEGF in neural cells commencing birth. Since astrocytes and neurons are main producers of VEGF in the brain after birth, this genetic model will allow us to test the putative role of VEGF in adult neural stem cell function. Our previous findings also suggest, that the neurogenic effect of VEGF is mediated by VEGF-R2. To rule out a possible role of the other tyrosine kinase receptor for VEGF, VEGF-R1, we plan to investigate mice with a homozygous deletion of the placenta growth factor gene (P1GF). P1GF only binds to VEGFR-1 but not to VEGFR-2, in contrast to VEGF, which binds to VEGFR-1 and -R-2. Taken together, these two transgenic mouse models will allow us to dissect the putative role VEGF may have in adult neural stem cells and to identify the receptors involved.