Induction of superficial cortical layer neurons from mouse embryonic stem cells by valproic acid

Berry Juliandi, Masahiko Abematsu, Tsukasa Sanosaka, Keita Tsujimura, Austin Smith, Kinichi Nakashima

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Within the developing mammalian cortex, neural progenitors first generate deep-layer neurons and subsequently more superficial-layer neurons, in an inside-out manner. It has been reported recently that mouse embryonic stem cells (mESCs) can, to some extent, recapitulate cortical development in vitro, with the sequential appearance of neurogenesis markers resembling that in the developing cortex. However, mESCs can only recapitulate early corticogenesis; superficial-layer neurons, which are normally produced in later developmental periods in vivo, are under-represented. This failure of mESCs to reproduce later corticogenesis in vitro implies the existence of crucial factor(s) that are absent or uninduced in existing culture systems. Here we show that mESCs can give rise to superficial-layer neurons efficiently when treated with valproic acid (VPA), a histone deacetylase inhibitor. VPA treatment increased the production of Cux1-positive superficial-layer neurons, and decreased that of Ctip2-positive deep-layer neurons. These results shed new light on the mechanisms of later corticogenesis.

Original languageEnglish
Pages (from-to)23-31
Number of pages9
JournalNeuroscience Research
Volume72
Issue number1
DOIs
Publication statusPublished - 2012 Jan 1
Externally publishedYes

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Keywords

  • Corticogenesis
  • HDAC inhibitor
  • Histone acetylation
  • MESCs
  • Neurogenesis
  • Valproic acid

ASJC Scopus subject areas

  • Neuroscience(all)

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