title: Stage-specific requirement for cyclin D1 in glial progenitor cells of the cerebral cortex.
abstract: Despite the vast abundance of glial progenitor cells in the mouse brain parenchyma, little is known about the molecular mechanisms driving their proliferation in the adult. Here we unravel a critical role of the G1 cell cycle regulator cyclin D1 in controlling cell division of glial cells in the cortical grey matter. We detect cyclin D1 expression in Olig2-immunopositive (Olig2+) oligodendrocyte progenitor cells, as well as in Iba1+ microglia and S100β+ astrocytes in cortices of 3-month-old mice. Analysis of cyclin D1-deficient mice reveals a cell and stage-specific molecular control of cell cycle progression in the various glial lineages. While proliferation of fast dividing Olig2+ cells at early postnatal stages becomes gradually dependent on cyclin D1, this particular G1 regulator is strictly required for the slow divisions of Olig2+/NG2+ oligodendrocyte progenitors in the adult cerebral cortex. Further, we find that the population of mature oligodendrocytes is markedly reduced in the absence of cyclin D1, leading to a significant decrease in the number of myelinated axons in both the prefrontal cortex and the corpus callosum of 8-month-old mutant mice. In contrast, the pool of Iba1+ cells is diminished already at postnatal day 3 in the absence of cyclin D1, while the number of S100β+ astrocytes remains unchanged in the mutant.
authors.affiliation: Department of Biomedicine, Institute of Physiology, University of Basel, Basel, Switzerland.
authors.forename: Lionel
authors.initials: L
authors.lastname: Nobs
authors.forename: Constanze
authors.initials: C
authors.lastname: Baranek
authors.forename: Sigrun
authors.initials: S
authors.lastname: Nestel
authors.forename: Akos
authors.initials: A
authors.lastname: Kulik
authors.forename: Josef
authors.initials: J
authors.lastname: Kapfhammer
authors.forename: Cordula
authors.initials: C
authors.lastname: Nitsch
authors.forename: Suzana
authors.initials: S
authors.lastname: Atanasoski
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002455:Cell Division / Q000502:physiology; D002540:Cerebral Cortex / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism*; D019938:Cyclin D1 / Q000096:biosynthesis*; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009457:Neuroglia / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism*
chemical_list: C530105:Ccnd1 protein, mouse; D019938:Cyclin D1
keywords: astrocytes; cell cycle; cerebral cortex; microglia; oligodendrocyte progenitor cells; proliferation