Selection of differentiating cells by different levels of delta-like 1 among neural precursor cells in the developing mouse telencephalon

Daichi Kawaguchi, Takeshi Yoshimatsu, Katsuto Hozumi, Yukiko Gotoh

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

Abstract

During the neurogenic phase of mammalian brain development, only a subpopulation of neural precursor cells (NPCs) differentiates into neurons. The mechanisms underlying this selection remain unclear. Here we provide evidence that the Notch- Delta pathway plays an important role in this selection in the developing mouse telencephalon. We found that the expression patterns of the Notch ligand delta-like 1 (Dll1) and of the active form of Notch1 were mutually exclusive and segregated into distinct NPC subpopulations in the ventricular zone of the telencephalon. When Dll1 was overexpressed in a small, but not a large, proportion of NPCs, these cells underwent neuronal differentiation in vitro and in vivo. This Dll1-induced neuronal differentiation did not occur when cells were plated at lower densities in an in vitro culture. Importantly, conditional deletion of the Dll1 gene in a small proportion of NPCs reduced neurogenesis in vivo, whereas deletion in a large proportion promoted premature neurogenesis. These results support the notion that different levels of Dll1 expression determine the fate of NPCs through cell-cell interactions, most likely through the Notch-Delta lateral inhibitory signaling pathway, thus contributing to the selection of differentiating cells.

Original languageEnglish
Pages (from-to)3849-3858
Number of pages10
JournalDevelopment
Volume135
Issue number23
DOIs
StatePublished - Dec 1 2008

Keywords

  • Cell-cell interaction
  • DII1
  • Lateral inhibition
  • Neural precursor cell
  • Notch
  • Telencephalon

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