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

作者：Kawaguchi Daichi; Yoshimatsu Takeshi; Hozumi Katsuto; Gotoh Yukiko^*

来源：Development, 2008, 135(23): 3849-3858.

DOI：10.1242/dev.024570

• Dll1
• Notch
• Lateral inhibition
• Cell-cell interaction
• Neural precursor cell
• Telencephalon

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.

• 出版日期2008-12-1