Committed Neuronal Precursors Confer Astrocytic Potential on Residual Neural Precursor Cells

Masakazu Namihira, Jun Kohyama, Katsunori Semi, Tsukasa Sanosaka, Benjamin Deneen, Tetsuya Taga, Kinichi Nakashima

Research output: Contribution to journalArticle

213 Citations (Scopus)

Abstract

During midgestation, mammalian neural precursor cells (NPCs) differentiate only into neurons. Generation of astrocytes is prevented at this stage, because astrocyte-specific gene promoters are methylated. How the subsequent switch from suppression to expression of astrocytic genes occurs is unknown. We show in this study that Notch ligands are expressed on committed neuronal precursors and young neurons in mid-gestational telencephalon, and that neighboring Notch-activated NPCs acquire the potential to become astrocytes. Activation of the Notch signaling pathway in midgestational NPCs induces expression of the transcription factor nuclear factor I, which binds to astrocytic gene promoters, resulting in demethylation of astrocyte-specific genes. These findings provide a mechanistic explanation for why neurons come first: committed neuronal precursors and young neurons potentiate remaining NPCs to differentiate into the next cell lineage, astrocytes.

Original languageEnglish
Pages (from-to)245-255
Number of pages11
JournalDevelopmental Cell
Volume16
Issue number2
DOIs
Publication statusPublished - 2009 Feb 17
Externally publishedYes

Keywords

  • DEVBIO
  • STEMCELL

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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