Cdk6-Dependent Regulation of G1 Length Controls Adult Neurogenesis§

Authors


  • Disclosure of potential conflicts of interest is found at the end of this article.

  • Author contribution: P.B. and R.V.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing; N.C.: collection and/or assembly of data, data analysis and interpretation; L.N.: data analysis and interpretation, critical review of the manuscript; S.B. and G.M.: financial support, critical review of the manuscript; H.K. and M.B.: provision of study material; D.S.: provision of study material, conception and design, data analysis and interpretation, critical review of the manuscript; B.M.: conception and design, financial support, data analysis and interpretation, final approval of the manuscript. *P.B. and R.V. contributed equally to this work.

  • §

    First published online in STEM CELLSEXPRESS February 11, 2011.

Abstract

The presence of neurogenic precursors in the adult mammalian brain is now widely accepted, but the mechanisms coupling their proliferation with the onset of neuronal differentiation remain unknown. Here, we unravel the major contribution of the G1 regulator cyclin-dependent kinase 6 (Cdk6) to adult neurogenesis. We found that Cdk6 was essential for cell proliferation within the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. Specifically, Cdk6 deficiency prevents the expansion of neuronally committed precursors by lengthening G1 phase duration, reducing concomitantly the production of newborn neurons. Altogether, our data support G1 length as an essential regulator of the switch between proliferation and neuronal differentiation in the adult brain and Cdk6 as one intrinsic key molecular regulator of this process. STEM Cells 2011;29:713–724

Ancillary