title: Btg1 is Required to Maintain the Pool of Stem and Progenitor Cells of the Dentate Gyrus and Subventricular Zone.
abstract: Btg1 belongs to a family of cell cycle inhibitory genes. We observed that Btg1 is highly expressed in adult neurogenic niches, i.e., the dentate gyrus and subventricular zone (SVZ). Thus, we generated Btg1 knockout mice to analyze the role of Btg1 in the process of generation of adult new neurons. Ablation of Btg1 causes a transient increase of the proliferating dentate gyrus stem and progenitor cells at post-natal day 7; however, at 2 months of age the number of these proliferating cells, as well as of mature neurons, greatly decreases compared to wild-type controls. Remarkably, adult dentate gyrus stem and progenitor cells of Btg1-null mice exit the cell cycle after completing the S phase, express p53 and p21 at high levels and undergo apoptosis within 5 days. In the SVZ of adult (two-month-old) Btg1-null mice we observed an equivalent decrease, associated to apoptosis, of stem cells, neuroblasts, and neurons; furthermore, neurospheres derived from SVZ stem cells showed an age-dependent decrease of the self-renewal and expansion capacity. We conclude that ablation of Btg1 reduces the pool of dividing adult stem and progenitor cells in the dentate gyrus and SVZ by decreasing their proliferative capacity and inducing apoptosis, probably reflecting impairment of the control of the cell cycle transition from G1 to S phase. As a result, the ability of Btg1-null mice to discriminate among overlapping contextual memories was affected. Btg1 appears, therefore, to be required for maintaining adult stem and progenitor cells quiescence and self-renewal.
authors.affiliation: Institute of Cell Biology and Neurobiology, National Research Council Fondazione Santa Lucia, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Farioli-Vecchioli
authors.forename: Laura
authors.initials: L
authors.lastname: Micheli
authors.forename: Daniele
authors.initials: D
authors.lastname: Saraulli
authors.forename: Manuela
authors.initials: M
authors.lastname: Ceccarelli
authors.forename: Sara
authors.initials: S
authors.lastname: Cannas
authors.forename: Raffaella
authors.initials: R
authors.lastname: Scardigli
authors.forename: Luca
authors.initials: L
authors.lastname: Leonardi
authors.forename: Irene
authors.initials: I
authors.lastname: Cinà
authors.forename: Marco
authors.initials: M
authors.lastname: Costanzi
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Ciotti
authors.forename: Pedro
authors.initials: P
authors.lastname: Moreira
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Rouault
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cestari
authors.forename: Felice
authors.initials: F
authors.lastname: Tirone