title: Cdk5 regulates accurate maturation of newborn granule cells in the adult hippocampus.
abstract: Newborn granule cells become functionally integrated into the synaptic circuitry of the adult dentate gyrus after a morphological and electrophysiological maturation process. The molecular mechanisms by which immature neurons and the neurites extending from them find their appropriate position and target area remain largely unknown. Here we show that single-cell-specific knockdown of cyclin-dependent kinase 5 (cdk5) activity in newborn cells using a retrovirus-based strategy leads to aberrant growth of dendritic processes, which is associated with an altered migration pattern of newborn cells. Even though spine formation and maturation are reduced in cdk5-deficient cells, aberrant dendrites form ectopic synapses onto hilar neurons. These observations identify cdk5 to be critically involved in the maturation and dendrite extension of newborn neurons in the course of adult neurogenesis. The data presented here also suggest a mechanistic dissociation between accurate dendritic targeting and subsequent synapse formation.
authors.affiliation: Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California, USA. jessberger@cell.biol.ethz.ch
authors.forename: Sebastian
authors.initials: S
authors.lastname: Jessberger
authors.forename: Stefan
authors.initials: S
authors.lastname: Aigner
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Clemenson
authors.forename: Nicolas
authors.initials: N
authors.lastname: Toni
authors.forename: D Chichung
authors.initials: DC
authors.lastname: Lie
authors.forename: Ozlem
authors.initials: O
authors.lastname: Karalay
authors.forename: Rupert
authors.initials: R
authors.lastname: Overall
authors.forename: Gerd
authors.initials: G
authors.lastname: Kempermann
authors.forename: Fred H
authors.initials: FH
authors.lastname: Gage
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology; D000818:Animals; D002454:Cell Differentiation; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics / Q000378:metabolism*; D003712:Dendrites / Q000502:physiology; D018891:Dentate Gyrus / Q000166:cytology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000166:cytology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D051381:Rats; D012190:Retroviridae / Q000235:genetics; D013569:Synapses / Q000502:physiology
chemical_list: D051360:Cyclin-Dependent Kinase 5