Histone deacetylases 1 and 2 control the progression of neural precursors to neurons during brain development.
The molecular mechanism by which neural progenitor cells commit to a specified lineage of the central nervous system remains unknown. We show that HDAC1 and HDAC2 redundantly control neuronal development and are required for neuronal specification. Mice lacking HDAC1 or HDAC2 in neuronal precursors show no overt histoarchitectural phenotypes, whereas deletion of both HDAC1 and HDAC2 in developing neurons results in severe hippocampal abnormalities, absence of cerebellar foliation, disorganization of cortical neurons, and lethality by postnatal day 7. These abnormalities in brain formation can be attributed to a failure of neuronal precursors to differentiate into mature neurons and to excessive cell death. These results reveal redundant and essential roles for HDAC1 and HDAC2 in the progression of neuronal precursors to mature neurons in vivo.
Montgomery
Rusty L
RL
Department of Molecular Biology, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390-9148, USA.
Hsieh
Jenny
J
Barbosa
Ana C
AC
Richardson
James A
JA
Olson
Eric N
EN
D000483:Alleles; D000818:Animals; D001921:Brain / Q000196:embryology*; D002454:Cell Differentiation; D002465:Cell Movement; D002540:Cerebral Cortex / Q000378:metabolism; D017353:Gene Deletion; D006624:Hippocampus / Q000196:embryology; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000502:physiology*; D051379:Mice; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D010641:Phenotype; D012097:Repressor Proteins / Q000502:physiology*
D056572:Histone Deacetylase Inhibitors; D012097:Repressor Proteins; C484389:Hdac1 protein, mouse; C533424:Hdac2 protein, mouse; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases