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LS_8<br />

Functional role of Vav3 for the regulation and<br />

differentiation of neural stem/ progenitor cells in the<br />

developing visual system<br />

Veronika Luft 1,2 , Klaus-Dieter Fischer 4 , Ulf Eysel 2,3 , Andreas Faissner 1,2<br />

1<br />

Department of Cell Morphology and Molecular Neurobiology, Ruhr University Bochum,<br />

Germany<br />

2<br />

International Graduate <strong>School</strong> of Neuroscience, Ruhr University Bochum, Germany<br />

3<br />

Neurophysiology, Department of Medicine, Ruhr University Bochum, Germany<br />

4<br />

Institute of Biochemistry and Cell Biology, Otto-von-Guericke-University Magdeburg,<br />

Germany<br />

e-mail: Veronika.Luft@rub.de<br />

Chondroitinsulfate proteoglycans (CSPGs) are highly enriched extracellular matrix (ECM)<br />

components in the developing ventricular zone. The degradation of their covalently attached<br />

gylcosaminoglycan chains induces a switch from neurogenic to gliogenic differentiation,<br />

diminishing neuronal progenitors and their progeny while simultaneously promoting<br />

astrocytic development. But the mechanisms, by which CSPGs regulate the proliferation and<br />

differentiation of neural stem cells, are still unknown. Previous experiments showed that<br />

digestion of glycosaminoglycans with the enzyme chondroitinase ABC leads to the upregulation<br />

of Vav3, an activator of RhoGTPases. In order to investigate the potential role of<br />

Vav3 for mediation of CSPG-dependent signalling in neural stem cells, we focused on the<br />

visual system of Vav3 -/- mice. Here, we analysed the expression pattern of Vav3 during<br />

embryonic and postnatal development. The cellular composition of the embryonic retina and<br />

cortex in Vav3 deficient mice was investigated in vitro and in vivo. And finally, our analysis<br />

revealed differences in the differentiation capacity of Vav3 deficient neurospheres.<br />

Together, we conclude that Vav3 potentially interferes with the proliferation and<br />

differentiation of neural stem cells and that its loss leads to an immature phenotype. This<br />

study will probably lead to a better understanding of the role of CSPGs on stem cell<br />

behaviour.

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