Repressor element 1 silencing transcription factor (REST) controls radial migration and temporal neuronal specification during neocortical development

Gail Mandel, Christopher G. Fiondella, Matthew V. Covey, Diane D. Lu, Joseph J. LoTurco, Nurit Ballas

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Neurogenesis requires mechanisms that coordinate early cell-fate decisions, migration, and terminal differentiation. Here, we show that the transcriptional repressor, repressor element 1 silencing transcription factor (REST), regulates radial migration and the timing of neural progenitor differentiation during neocortical development, and that the regulation is contingent upon differential REST levels. Specifically, a sustained presence of REST blocks migration and greatly delays - but does not prevent - neuronal differentiation, resulting in a subcortical band heterotopia-like phenotype, reminiscent of loss of doublecortin. We further show that double-cortin is a direct gene target of REST, and that its overexpression rescues, at least in part, the aberrant phenotype caused by persistent presence of REST. Our studies support the view that the targeted down-regulation of REST to low levels in neural progenitors, and its subsequent disappearance during neurogenesis, is critical for timing the spatiotemporal transition of neural progenitor cells to neurons.

Original languageEnglish (US)
Pages (from-to)16789-16794
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number40
DOIs
StatePublished - Oct 4 2011

Keywords

  • In utero electroporation
  • Neuronal cell fate
  • Neuronal differentiation

ASJC Scopus subject areas

  • General

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