title: Cdk6-dependent regulation of G(1) length controls adult neurogenesis.
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 G(1) 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 G(1) phase duration, reducing concomitantly the production of newborn neurons. Altogether, our data support G(1) 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.
authors.affiliation: GIGA-Neurosciences, University of Liège, Liège, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Beukelaers
authors.forename: Renaud
authors.initials: R
authors.lastname: Vandenbosch
authors.forename: Nicolas
authors.initials: N
authors.lastname: Caron
authors.forename: Laurent
authors.initials: L
authors.lastname: Nguyen
authors.forename: Shibeshih
authors.initials: S
authors.lastname: Belachew
authors.forename: Gustave
authors.initials: G
authors.lastname: Moonen
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kiyokawa
authors.forename: Mariano
authors.initials: M
authors.lastname: Barbacid
authors.forename: David
authors.initials: D
authors.lastname: Santamaria
authors.forename: Brigitte
authors.initials: B
authors.lastname: Malgrange
mesh_terms: D000375:Aging; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D049109:Cell Proliferation; D051358:Cyclin-Dependent Kinase 4 / Q000096:biosynthesis / Q000235:genetics; D051361:Cyclin-Dependent Kinase 6 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D018891:Dentate Gyrus / Q000166:cytology / Q000196:embryology; D005455:Fluorescent Antibody Technique; D016193:G1 Phase; D020547:Lateral Ventricles / Q000166:cytology / Q000196:embryology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000502:physiology
chemical_list: C495902:Cdk4 protein, mouse; C495912:Cdk6 protein, mouse; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6