Cdk5 regulates accurate maturation of newborn granule cells in the adult hippocampus.
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.
Jessberger
Sebastian
S
Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California, USA. jessberger@cell.biol.ethz.ch
Aigner
Stefan
S
Clemenson
Gregory D
GD
Toni
Nicolas
N
Lie
D Chichung
DC
Karalay
Ozlem
O
Overall
Rupert
R
Kempermann
Gerd
G
Gage
Fred H
FH
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
D051360:Cyclin-Dependent Kinase 5