CoREST/LSD1 control the development of pyramidal cortical neurons

Patricio Fuentes, José Cánovas, F. Andrés Berndt, Stephen C Noctor, Manuel Kukuljan

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

The development of a neuron from a precursor cell comprises a complex set of steps ranging from regulation of the proliferative cycle through the acquisition of distinct morphology and functionality. How these processes are orchestrated is largely unknown. Using in utero manipulation of gene expression in the mouse embryonic cerebral cortex, we found that the transition between multipolar and bipolar stages of newborn cortical pyramidal neurons is markedly delayed by depletion of CoREST, a corepressor component of chromatin remodeling complexes. This profoundly affects the onset of their radial migration. The loss of CoREST function also perturbs the dynamics of neuronal precursor cell populations, transiently increasing the fraction of cells remaining in progenitor states, but not the acquisition of the neuronal glutamatergic fate of pyramidal cells. The function of CoREST in these processes appears to be independent of its best-known interactor, the RE-1 silencer of transcription/neural restrictive silencing factor, and requires the histone demethylase LSD1. This reveals the importance of epigenetic control in the execution of neural development programs, specifically in the cerebral cortex.

Original languageEnglish (US)
Pages (from-to)1431-1441
Number of pages11
JournalCerebral Cortex
Volume22
Issue number6
DOIs
StatePublished - Jun 2012

Keywords

  • epigenetic regulation
  • migration
  • neuronal progenitor

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

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