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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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 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.

Detaljer

Författare
  • Beata Jablonska
  • Adan Aguirre
  • Renaud Vandenbosch
  • Shibeshih Belachew
  • Cyril Berthet
  • Philipp Kaldis
  • Vittorio Gallo
Externa organisationer
  • Children’s National Health System, Washington
  • University of Liège
  • National Cancer Institute at Frederick
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Cell- och molekylärbiologi
Originalspråkengelska
Sidor (från-till)1231-1245
Antal sidor15
TidskriftJournal of Cell Biology
Volym179
Utgåva nummer6
StatusPublished - 2007 dec 17
PublikationskategoriForskning
Peer review utfördJa
Externt publiceradJa