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

Development. 2008 Dec;135(23):3849-58. doi: 10.1242/dev.024570.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Patterning
  • Calcium-Binding Proteins
  • Cell Communication
  • Cell Differentiation*
  • Cell Lineage
  • Gene Deletion
  • Gene Expression Regulation, Developmental
  • Intercellular Signaling Peptides and Proteins / chemistry
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Mice
  • Mice, Inbred ICR
  • Neocortex / cytology
  • Neocortex / embryology
  • Neocortex / metabolism
  • Neurogenesis
  • Neurons / cytology*
  • Neurons / metabolism
  • Protein Structure, Tertiary
  • Receptor, Notch1 / genetics
  • Receptor, Notch1 / metabolism
  • Stem Cells / cytology*
  • Stem Cells / metabolism
  • Telencephalon / cytology*
  • Telencephalon / embryology*
  • Telencephalon / metabolism

Substances

  • Calcium-Binding Proteins
  • Dlk1 protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • Receptor, Notch1