Histone deacetylases 1 and 2 control the progression of neural precursors to neurons during brain development

Rusty L. Montgomery, Jenny Hsieh, Ana C. Barbosa, James A Richardson, Eric N Olson

Research output: Contribution to journalArticlepeer-review

224 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)7876-7881
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number19
DOIs
StatePublished - May 12 2009

Keywords

  • Cerebellum
  • Hippocampus
  • Neurogenesis
  • Neuronal precursors

ASJC Scopus subject areas

  • General

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