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Published online December 17, 2007
doi:10.1083/jcb.200702031
The Journal of Cell Biology, Vol. 179, No. 6, 1231-1245
The Rockefeller University Press, 0021-9525 $30.00
© 2007 Jablonska et al.
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Article

 Cdk2 is critical for proliferation and self-renewal of neural progenitor cells in the adult subventricular zone

Beata Jablonska1, Adan Aguirre1, Renaud Vandenbosch2, Shibeshih Belachew2, Cyril Berthet3, Philipp Kaldis3, and Vittorio Gallo1

1 Center for Neuroscience Research, Children's National Medical Center, Washington, DC 20010
2 Department of Neurology, Center for Cellular and Molecular Neurobiology, University of Liege, 4000 Liege, Belgium
3 Mouse Cancer Genetics Program, National Cancer Institute, Frederick, MD 21702

Correspondence to V. Gallo: vgallo{at}cnmcresearch.org

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.

Abbreviations used in this paper: ASVZ, anterior SVZ; Dcx, doublecortin; GalC, galactocerebroside; GFAP, glial fibrillary acidic protein; LSVZ, lateral SVZ; MAP2, microtubule-associated protein 2; P, postnatal day; Rb, retinoblastoma protein; RMS, rostral migratory stream; SCM, stem cell medium; SVZ, subventricular zone.


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