Cdk2 is critical for proliferation and self-renewal of neural progenitor cells in the adult subventricular zone
Jablonska, Beata ; Aguirre, Adan ; Vandenbosch, Renaud ; Belachew, Shibeshih ; Berthet, Cyril ; Kaldis, Philipp LU
and Gallo, Vittorio
(2007)
In Journal of Cell Biology
179(6).
p.1231-1245
- Abstract
We investigated the function of cyclin-dependent kinase 2 (Cdk2) in neural progenitor cells during postnatal development. Chondroitin sulfate proteoglycan (NG2)-expressing progenitor cells of the subventricular zone (SVZ) show no significant difference in density and proliferation between Cdk2-/- and wild-type mice at perinatal ages and are reduced only in adult Cdk2 -/- mice. Adult Cdk2-/- SVZ cells in culture display decreased self-renewal capacity and enhanced differentiation. Compensatory mechanisms in perinatal Cdk2-/- SVZ cells, which persist until postnatal day 15, involve increased Cdk4 expression that results in retinoblastoma protein inactivation. A subsequent decline in Cdk4... (More)
We investigated the function of cyclin-dependent kinase 2 (Cdk2) in neural progenitor cells during postnatal development. Chondroitin sulfate proteoglycan (NG2)-expressing progenitor cells of the subventricular zone (SVZ) show no significant difference in density and proliferation between Cdk2-/- and wild-type mice at perinatal ages and are reduced only in adult Cdk2 -/- mice. Adult Cdk2-/- SVZ cells in culture display decreased self-renewal capacity and enhanced differentiation. Compensatory mechanisms in perinatal Cdk2-/- SVZ cells, which persist until postnatal day 15, involve increased Cdk4 expression that results in retinoblastoma protein inactivation. A subsequent decline in Cdk4 activity to wild-type levels in postnatal day 28 Cdk2-/- cells coincides with lower NG2+ proliferation and self-renewal capacity similar to adult levels. Cdk4 silencing in perinatal Cdk2-/- SVZ cells abolishes Cdk4 up-regulation and reduces cell proliferation and self-renewal to adult levels. Conversely, Cdk4 overexpression in adult SVZ cells restores proliferative capacity to wild-type levels. Thus, although Cdk2 is functionally redundant in perinatal SVZ, it is important for adult progenitor cell proliferation and self-renewal through age-dependent regulation of Cdk4.
(Less)
- author
- Jablonska, Beata
; Aguirre, Adan
; Vandenbosch, Renaud
; Belachew, Shibeshih
; Berthet, Cyril
; Kaldis, Philipp
LU
and Gallo, Vittorio
- publishing date
- 2007-12-17
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Cell Biology
- volume
- 179
- issue
- 6
- pages
- 15 pages
- publisher
- Rockefeller University Press
- external identifiers
-
- scopus:37249050507
- pmid:18086919
- ISSN
- 0021-9525
- DOI
- 10.1083/jcb.200702031
- language
- English
- LU publication?
- no
- id
- 6a43ee71-7463-4b25-a612-93afc927940d
- date added to LUP
- 2019-09-18 14:15:24
- date last changed
- 2024-04-02 16:53:07
@article{6a43ee71-7463-4b25-a612-93afc927940d,
abstract = {{<p>We investigated the function of cyclin-dependent kinase 2 (Cdk2) in neural progenitor cells during postnatal development. Chondroitin sulfate proteoglycan (NG2)-expressing progenitor cells of the subventricular zone (SVZ) show no significant difference in density and proliferation between Cdk2<sup>-/-</sup> and wild-type mice at perinatal ages and are reduced only in adult Cdk2 <sup>-/-</sup> mice. Adult Cdk2<sup>-/-</sup> SVZ cells in culture display decreased self-renewal capacity and enhanced differentiation. Compensatory mechanisms in perinatal Cdk2<sup>-/-</sup> SVZ cells, which persist until postnatal day 15, involve increased Cdk4 expression that results in retinoblastoma protein inactivation. A subsequent decline in Cdk4 activity to wild-type levels in postnatal day 28 Cdk2<sup>-/-</sup> cells coincides with lower NG2<sup>+</sup> proliferation and self-renewal capacity similar to adult levels. Cdk4 silencing in perinatal Cdk2<sup>-/-</sup> SVZ cells abolishes Cdk4 up-regulation and reduces cell proliferation and self-renewal to adult levels. Conversely, Cdk4 overexpression in adult SVZ cells restores proliferative capacity to wild-type levels. Thus, although Cdk2 is functionally redundant in perinatal SVZ, it is important for adult progenitor cell proliferation and self-renewal through age-dependent regulation of Cdk4.</p>}},
author = {{Jablonska, Beata and Aguirre, Adan and Vandenbosch, Renaud and Belachew, Shibeshih and Berthet, Cyril and Kaldis, Philipp and Gallo, Vittorio}},
issn = {{0021-9525}},
language = {{eng}},
month = {{12}},
number = {{6}},
pages = {{1231--1245}},
publisher = {{Rockefeller University Press}},
series = {{Journal of Cell Biology}},
title = {{Cdk2 is critical for proliferation and self-renewal of neural progenitor cells in the adult subventricular zone}},
url = {{http://dx.doi.org/10.1083/jcb.200702031}},
doi = {{10.1083/jcb.200702031}},
volume = {{179}},
year = {{2007}},
}