title: Cyclin D1 is required for proliferation of Olig2-expressing progenitor cells in the injured cerebral cortex.
abstract: Little is known about the molecular mechanisms driving proliferation of glial cells after an insult to the central nervous system (CNS). To test the hypothesis that the G1 regulator cyclin D1 is critical for injury-induced cell division of glial cells, we applied an injury model that causes brain damage within a well-defined region. For this, we injected the neurotoxin ibotenic acid into the prefrontal cortex of adult mice, which leads to a local nerve cell loss but does not affect the survival of glial cells. Here, we show that cyclin D1 immunoreativity increases drastically after neurotoxin injection. We find that the cyclin D1-immunopositive (cyclin D1+) cell population within the lesioned area consists to a large extent of Olig2+ oligodendrocyte progenitor cells. Analysis of cyclin D1-deficient mice demonstrates that the proliferation rate of Olig2+ cells diminishes upon loss of cyclin D1. Further, we show that cyclin-dependent kinase (cdk) 4, but not cdk6 or cdk2, is essential for driving cell division of Olig2-expressing cells in our injury model. These data suggest that distinct cell cycle proteins regulate proliferation of Olig2+ progenitor cells following a CNS insult.
authors.affiliation: Institute of Physiology, Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Lionel
authors.initials: L
authors.lastname: Nobs
authors.forename: Sigrun
authors.initials: S
authors.lastname: Nestel
authors.forename: Akos
authors.initials: A
authors.lastname: Kulik
authors.forename: Cordula
authors.initials: C
authors.lastname: Nitsch
authors.forename: Suzana
authors.initials: S
authors.lastname: Atanasoski
mesh_terms: D053687:Adult Stem Cells / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D001930:Brain Injuries / Q000473:pathology*; D001973:Bromodeoxyuridine; D049109:Cell Proliferation / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D019938:Cyclin D1 / Q000172:deficiency / Q000378:metabolism*; D051357:Cyclin-Dependent Kinase 2 / Q000172:deficiency; D051358:Cyclin-Dependent Kinase 4 / Q000172:deficiency; D051361:Cyclin-Dependent Kinase 6 / Q000172:deficiency; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D007051:Ibotenic Acid / Q000633:toxicity; D020287:In Situ Nick-End Labeling; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009498:Neurotoxins / Q000633:toxicity; D000076104:Oligodendrocyte Transcription Factor 2; D013997:Time Factors
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D001973:Bromodeoxyuridine; D019938:Cyclin D1; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6; D007051:Ibotenic Acid; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D000076104:Oligodendrocyte Transcription Factor 2; C530105:Ccnd1 protein, mouse; C512773:Olig2 protein, mouse; C495893:Cdk2 protein, mouse; C495902:Cdk4 protein, mouse; C495912:Cdk6 protein, mouse
keywords: brain injuries; cell cycle; glial progenitor cells; proliferation