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 gener- ation 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 com- pared 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, neu- roblasts, and neurons; furthermore, neurospheres derived from SVZ stem cells showed an age-
Btg1 is Required to Maintain the Pool of Stem and Progenitor Cells of the Dentate Gyrus and Subventricular Zone / Farioli Vecchioli, S; Micheli, L; Saraulli, Daniele; Ceccarelli, M; Cannas, S; Scardigli, R; Leonardi, L; Cinà, I; Costanzi, M; Ciotti, Mt; Moreira, P; Rouault, Jp; Cestari, Vincenzo; Tirone, F.. - In: FRONTIERS IN NEUROSCIENCE. - ISSN 1662-453X. - ELETTRONICO. - 6:(2012), pp. 1-19. [10.3389/fnins.2012.00124]
Btg1 is Required to Maintain the Pool of Stem and Progenitor Cells of the Dentate Gyrus and Subventricular Zone.
SARAULLI, DANIELE;CESTARI, VINCENZO;
2012
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 gener- ation 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 com- pared 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, neu- roblasts, and neurons; furthermore, neurospheres derived from SVZ stem cells showed an age-I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.