<i>Dlk1</i> dosage regulates hippocampal neurogenesis and cognition
Raquel Montalbán-Loro, Glenda Lassi, Anna Lozano-Ureña, Ana Pérez‐Villalba, Esteban Jiménez-Villalba, Marika Charalambous, Giorgio Vallortígara, Alexa E. Horner, Lisa M. Saksida, Timothy J. Bussey, José Luís Trejo, Valter Tucci, Anne C. Ferguson‐Smith, Sacri R. Ferrón
Abstract
Significance Generation of new neurons occurs normally in the adult brain in two locations: the subventricular zone (SVZ) in the walls of the lateral ventricles and the subgranular zone (SGZ) in the dentate gyrus (DG) of the hippocampus. Neurogenesis in the adult hippocampus has been implicated in cognitive functions such as learning, memory, and recovery of stress response. Imprinted genes are highly prevalent in the brain and have adult and developmental important functions. Genetic deletion of the imprinted gene Dlk1 from either parental allele shows that DLK1 is a key mediator of quiescence in adult hippocampal NSCs. Additionally, Dlk1 is exquisitely dosage sensitive in the brain with perturbations in levels resulting in impaired NSCs function and cognitive phenotypes.