The Gs-Linked Receptor GPR3 Inhibits the Proliferation of Cerebellar Granule Cells during Postnatal Development

Hdl Handle:
http://hdl.handle.net/10675.2/569
Title:
The Gs-Linked Receptor GPR3 Inhibits the Proliferation of Cerebellar Granule Cells during Postnatal Development
Authors:
Tanaka, Shigeru; Shaikh, Imran Mohammed; Chiocca, Ennio Antonio; Saeki, Yoshinaga
Abstract:
Background: During postnatal murine and rodent cerebellar development, cerebellar granule precursors (CGP) gradually stop proliferating as they differentiate after migration to the internal granule layer (IGL). Molecular events that govern this program remain to be fully elucidated. GPR3 belongs to a family of Gs-linked receptors that activate cyclic AMP and are abundantly expressed in the adult brain.; Methodology/Principal Findings: To investigate the role of this orphan receptor in CGP differentiation, we determined that exogenous GPR3 expression in rat cerebellar granule neurons partially antagonized the proliferative effect of Sonic hedgehog (Shh), while endogenous GPR3 inhibition by siRNA stimulated Shh-induced CGP proliferation. In addition, exogenous GPR3 expression in CGPs correlated with increased p27/kip expression, while GPR3 knock-down led to a decrease in p27/kip expression. In wild-type mice, GPR3 expression increased postnatally and its expression was concentrated in the internal granular layer (IGL). In GPR3 â /â mice, the IGL was widened with increased proliferation of CGPs, as measured by bromodeoxyuridine incorporation. Cell cycle kinetics of GPR3-transfected medulloblastoma cells revealed a G0/G1 block, consistent with cell cycle exit.; Conclusions/Significance: These results thus indicate that GPR3 is a novel antiproliferative mediator of CGPs in the postnatal development of murine cerebellum.
Editors:
Mei, Lin
Citation:
PLoS ONE. 2009 Jun 15; 4(6):e5922
Issue Date:
15-Jun-2009
URI:
http://hdl.handle.net/10675.2/569
DOI:
10.1371/journal.pone.0005922
PubMed ID:
19526062
PubMed Central ID:
PMC2691605
Type:
Article
ISSN:
1932-6203
Appears in Collections:
Department of Neurology: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorTanaka, Shigeruen_US
dc.contributor.authorShaikh, Imran Mohammeden_US
dc.contributor.authorChiocca, Ennio Antonioen_US
dc.contributor.authorSaeki, Yoshinagaen_US
dc.contributor.editorMei, Lin-
dc.date.accessioned2012-10-26T16:26:43Z-
dc.date.available2012-10-26T16:26:43Z-
dc.date.issued2009-06-15en_US
dc.identifier.citationPLoS ONE. 2009 Jun 15; 4(6):e5922en_US
dc.identifier.issn1932-6203en_US
dc.identifier.pmid19526062en_US
dc.identifier.doi10.1371/journal.pone.0005922en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/569-
dc.description.abstractBackground: During postnatal murine and rodent cerebellar development, cerebellar granule precursors (CGP) gradually stop proliferating as they differentiate after migration to the internal granule layer (IGL). Molecular events that govern this program remain to be fully elucidated. GPR3 belongs to a family of Gs-linked receptors that activate cyclic AMP and are abundantly expressed in the adult brain.en_US
dc.description.abstractMethodology/Principal Findings: To investigate the role of this orphan receptor in CGP differentiation, we determined that exogenous GPR3 expression in rat cerebellar granule neurons partially antagonized the proliferative effect of Sonic hedgehog (Shh), while endogenous GPR3 inhibition by siRNA stimulated Shh-induced CGP proliferation. In addition, exogenous GPR3 expression in CGPs correlated with increased p27/kip expression, while GPR3 knock-down led to a decrease in p27/kip expression. In wild-type mice, GPR3 expression increased postnatally and its expression was concentrated in the internal granular layer (IGL). In GPR3 â /â mice, the IGL was widened with increased proliferation of CGPs, as measured by bromodeoxyuridine incorporation. Cell cycle kinetics of GPR3-transfected medulloblastoma cells revealed a G0/G1 block, consistent with cell cycle exit.en_US
dc.description.abstractConclusions/Significance: These results thus indicate that GPR3 is a novel antiproliferative mediator of CGPs in the postnatal development of murine cerebellum.en_US
dc.rightsTanaka et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.subjectResearch Articleen_US
dc.subjectNeuroscience/Neural Homeostasisen_US
dc.subjectNeuroscience/Neurobiology of Disease and Regenerationen_US
dc.subjectNeuroscience/Neurodevelopmenten_US
dc.subjectNeuroscience/Neuronal Signaling Mechanismsen_US
dc.titleThe Gs-Linked Receptor GPR3 Inhibits the Proliferation of Cerebellar Granule Cells during Postnatal Developmenten_US
dc.typeArticleen_US
dc.identifier.pmcidPMC2691605en_US
dc.contributor.corporatenameDepartment of Neurology-
dc.contributor.corporatenameCollege of Graduate Studies-

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