Nucleotide receptors govern proliferation and differentiation of human neural stem cells
Final Report Abstract
The study aimed at providing cues for improving the in vitro production of neurons, in particular of neurons with a dopaminergic phenotype. It was the goal of the project to analyse the functional expression of nucleotide receptors and their mechanistic role in affecting neural stem cell proliferation and differentiation in both human and mouse fetal neural stem cells. The project had proposed comparative and complementary approaches by using in parallel human (Leipzig) and mouse (Frankfurt) fetal neural progenitors. As a result of the reviewing process the human project (Leipzig) was excluded. Therefore the investigations were performed on mouse cells and in Frankfurt only. The data provide clear evidence that fetal mouse midbrain-derived neural precursors express a multitude of purinergic receptors and respond to a broad range of nucleotide receptor agonists. Nucleotides can be employed to enhance in vitro survival of young neurons and to increase the contribution of dopaminergic neurons to the total of precursor-derived neurons. Extracellular nucleotides can also negatively affect the survival of neurons in vitro. Our results demonstrate that nucleotides can be applied to enhance the formation of dopaminergic neurons from fetal mouse midbrain-derived neural precursors.
Publications
- Activationdependent trafficking of NTPDase2 in Chinese hamster ovary cells. Int J Biochem Cell Biol. 2007; 39: 810–7
Vlajkovic SM, Wang CJ, Soeller C, Zimmermann H, Thorne PR, Housley GD
(See online at https://doi.org/10.1016/j.biocel.2007.01.003) - Cloning, purification, and identification of the liver canalicular ecto-ATPase as NTPDase8. Am J Physiol Gastrointest Liver Physiol. 2007; 292: G785–95
Fausther M, Lecka J, Kukulski F, Lévesque SA, Pelletier J, Zimmermann H, Dranoff JA, Sévigny J
(See online at https://doi.org/10.1152/ajpgi.00293.2006) - Ectonucleotidases in Müller glial cells of the rodent retina: Involvement in inhibition of osmotic cell swelling. Purinergic Signal. 2007; 3: 423–33
Iandiev I, Wurm A, Pannicke T, Wiedemann P, Reichenbach A, Robson SC, Zimmermann H, Bringmann A
(See online at https://doi.org/10.1007/s11302-007-9061-3) - Ectonucleotidases, molecular properties and functional impact. An R Acad Nac Farm. 2007; 73: 537–66
Zimmermann H, Mishra SK, Shukla V, Lange D, Gampe K, Grimm I, Delic J, Braun N
- The ectonucleotidases alkaline phosphatase and nucleoside triphosphate diphosphohydrolase 2 are associated with subsets of progenitor cell populations in the mouse embryonic, postnatal and adult neurogenic zones. Neuroscience. 2007; 150: 863–79
Langer D, Ikehara Y, Takebayashi H, Hawkes R, Zimmermann H
(See online at https://doi.org/10.1016/j.neuroscience.2007.07.064) - Capillary electrophoresis-based nanoscale assays for monitoring ecto-5`-nucleotidase activity and inhibition in preparations of recombinant enzyme and melanoma cell membranes. Analyt Biochem. 2008; 373: 129–40
Iqbal J, Jirovsky D, Lee SJ, Zimmermann H, Müller CE
(See online at https://doi.org/10.1016/j.ab.2007.09.028) - Commentary: ATP and acetylcholine, equal brethren. Neurochem Int. 2008; 52: 634–48
Zimmermann H
(See online at https://doi.org/10.1016/j.neuint.2007.09.004) - Distribution of ectonucleotidasesin the rodent brain revisited. Cell Tissue Res. 2008; 334: 199–217
Langer D, Hammer K, Koszalka P, Schrader J, Robson S, Zimmermann H
(See online at https://doi.org/10.1007/s00441-008-0681-x) - Purinergic receptor activation inhibits osmotic glial cell swelling in the diabetic rat retina. Exp Eye Res. 2008; 87: 385–93
Wurm A, Inandiev I, Hollborn M, Wiedemann P, Reichenbach A, Zimmermann H, Bringmann A, Pannicke T
(See online at https://doi.org/10.1016/j.exer.2008.07.004) - Coordinate pathways for nucleotide and EGF signaling in cultured adult neural progenitor cells. J Cell Sci. 2009; 122: 2524–33
Grimm I, Messemer N, Stanke M, Gachet C, Zimmermann H
(See online at https://doi.org/10.1242/jcs.044891) - Purinergic Signaling in the nervous system: an overview. Trends Neurosci. 2009; 32: 19–29
Abbracchio MP, Burnstock G, Verkhratsky A, Zimmermann H
(See online at https://doi.org/10.1016/j.tins.2008.10.001) - Structure-activity relationships of anthraquinone derivatives derived from bromaminic acid as inhibitors of ectonucleoside triphosphate diphosphohydrolases (E-NTPDases). Purinergic Signal. 2009; 5: 91–106
Baqi Y, Weyler S, Iqbal J, Zimmermann H, Müller CE
(See online at https://doi.org/10.1007/s11302-008-9103-5) - The expanding field of purinergic signaling Trends Neurosci. 2009; 32: 1
Abbracchio MP, Burnstock G, Verkhratsky A, Zimmermann H
(See online at https://doi.org/10.1016/j.tins.2008.10.001) - Trophic functions of nucleotides in the central nervous system. Trends Neurosci. 2009; 32: 189–198
Neary JT, Zimmermann H
(See online at https://doi.org/10.1016/j.tins.2009.01.002)
