CoREST/LSD1 control the development of pyramidal cortical neurons

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 express...

Full description

Saved in:
Bibliographic Details
Published in:Cerebral cortex (New York, N.Y. 1991) N.Y. 1991), 2012-06, Vol.22 (6), p.1431-1441
Main Authors: Fuentes, Patricio, Cánovas, José, Berndt, F Andrés, Noctor, Stephen C, Kukuljan, Manuel
Format: Article
Language:English
Subjects:
Animals
Cell Movement - physiology
Cerebral Cortex - cytology
Cerebral Cortex - embryology
Epigenesis, Genetic - physiology
Female
Histone Demethylases
Membrane Proteins - physiology
Mice
Nerve Tissue Proteins - physiology
Neurogenesis - physiology
Neurons - physiology
Oxidoreductases, N-Demethylating - physiology
Pregnancy
Pyramidal Cells - embryology
Repressor Proteins - physiology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1047-3211
1460-2199
DOI:10.1093/cercor/bhr218