Nucleotide receptors govern proliferation and differentiation of human neural stem cells

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Nucleotides such as UTP and ATP, are amongst the phylogenetically and ontogentically oldest neurotransmitters. Via nucleotide receptor activation they provide mitogenic and survival signals for various cell types, including neural stem cells, astrocytes and neurons. Neural stem cells are present in the mammalian embryonic, fetal and adult brain giving rise to neurons and glia. These cells can be readily isolated, expanded and differentiated in vitro. In this project, we wish to study human tissue specific neural stem cells and as an additional model system embryonic mouse neural stem cells because 1. human neural stem cells have the highest relevance for human disease and 2. human neural stem cells maintain a high proliferative potential after many months in vitro. On the other hand, mouse neural stem cells can be obtained from genetically engineered animals offering the advantages of mouse genetics. In a first collaborative effort we showed that activation of metabotropic nucleotide receptors promotes proliferation and dopaminergic differentiation of human neural stem cells. The goal of the proposed research is to further investigate the functional expression of nucleotide receptors and their mechanistic role in affecting neural stem cell proliferation and differentiation in both human and mouse embryonic neural stem cells. The study is expected to provide novel insight and practical improvement for the effective in vitro production of neurons with a defined transmitter (e. g. dopaminergic) phenotype.