The specific role of histone deacetylase 2 in adult neurogenesis.
Gene expression changes during cell differentiation are thought to be coordinated by histone modifications, but still little is known about the role of specific histone deacetylases (HDACs) in cell fate decisions in vivo. Here we demonstrate that the catalytic function of HDAC2 is required in adult, but not embryonic neurogenesis. While brain development and adult stem cell fate were normal upon conditional deletion of HDAC2 or in mice lacking the catalytic activity of HDAC2, neurons derived from both zones of adult neurogenesis die at a specific maturation stage. This phenotype is correlated with an increase in proliferation and the aberrant maintenance of proteins normally expressed only in progenitors, such as Sox2, also into some differentiating neurons, suggesting that HDAC2 is critically required to silence progenitor transcripts during neuronal differentiation of adult generated neurons. This cell-autonomous function of HDAC2 exclusively in adult neurogenesis reveals clear differences in the molecular mechanisms regulating neurogenesis during development and in adulthood.
Jawerka
Melanie
M
Institute for Stem Cell Research, HelmholtzZentrum Munich, German Research Center for Environmental Health, Neuherberg/Munich, Germany.
Colak
Dilek
D
Dimou
Leda
L
Spiller
Carmen
C
Lagger
Sabine
S
Montgomery
Rusty L
RL
Olson
Eric N
EN
Wurst
Wolfgang
W
Göttlicher
Martin
M
Götz
Magdalena
M
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D056464:Histone Deacetylase 2 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000201:enzymology*
C533424:Hdac2 protein, mouse; D056464:Histone Deacetylase 2