| Purinergic signaling regulates neural progenitor cell expansion and neurogenesis. | |
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MedLine Citation:
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PMID: 17188262 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Neural stem and progenitor cells typically exhibit a density-dependent survival and expansion, such that critical densities are required below which clonogenic progenitors are lost. This suggests that short-range autocrine factors may be critical for progenitor cell maintenance. We report here that purines drive the expansion of ventricular zone neural stem and progenitor cells, and that purine receptor activation is required for progenitor cells to be maintained as such. Neural progenitors expressed P2Y purinergic receptors and mobilized intracellular calcium in response to agonist. Receptor antagonists suppressed proliferation and permitted differentiation into neurons and glia in vitro, while subsequent removal of purinergic inhibition restored progenitor cell expansion. Real-time bioluminescence imaging of extracellular ATP revealed that the source of extracellular nucleotides are the progenitor cells themselves, which appear to release ATP in episodic burst events. Enzyme histochemistry of the adult rat brain for ectonucleotidase activity revealed that NTDPase, which acts to degrade active ATP and thereby clears it from areas of active purinergic transmission, was selectively localized to the subventricular zone and the dentate gyrus, regions in which neuronal differentiation proceeds from the progenitor cell pool. These data suggest that purine nucleotides act as proliferation signals for neural progenitor cells, and thereby serve as negative regulators of terminal neuronal differentiation. As a result, progenitor cell-derived neurogenesis is thus associated with regions of both active purinergic signaling and modulation thereof. |
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Authors:
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Jane H-C Lin; Takahiro Takano; Gregory Arcuino; Xiaohai Wang; Furong Hu; Zbigniew Darzynkiewicz; Marta Nunes; Steven A Goldman; Maiken Nedergaard |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2006-09-16 |
Journal Detail:
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Title: Developmental biology Volume: 302 ISSN: 0012-1606 ISO Abbreviation: Dev. Biol. Publication Date: 2007 Feb |
Date Detail:
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Created Date: 2007-01-22 Completed Date: 2007-03-06 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 0372762 Medline TA: Dev Biol Country: United States |
Other Details:
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Languages: eng Pagination: 356-66 Citation Subset: IM |
Affiliation:
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Department of Cell Biology, New York Medical College, Valhalla, NY, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Autocrine Communication Brain / metabolism Cell Differentiation Mice Mice, Inbred Strains Mitogens / metabolism Neurons / cytology*, metabolism Nucleotidases / metabolism Purinergic P2 Receptor Antagonists Purines / metabolism* Rats Receptors, Purinergic P2 / metabolism* Signal Transduction Stem Cells / cytology*, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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NS29813/NS/NINDS NIH HHS; NS33106/NS/NINDS NIH HHS; NS38073/NS/NINDS NIH HHS; NS39559/NS/NINDS NIH HHS; NS41031/NS/NINDS NIH HHS; R01 CA028704-27/CA/NCI NIH HHS; R01 NS030007-11A1/NS/NINDS NIH HHS; R01 NS041031-01A1/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Mitogens; 0/Purinergic P2 Receptor Antagonists; 0/Purines; 0/Receptors, Purinergic P2; EC 3.1.3.-/Nucleotidases; EC 3.1.3.31/nucleotidase |
| Comments/Corrections | |
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