Journal
DEVELOPMENT
Volume 135, Issue 23, Pages 3849-3858Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.024570
Keywords
Dll1; Notch; Lateral inhibition; Cell-cell interaction; Neural precursor cell; Telencephalon
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Funding
- Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan
- SORST from the Japan Science and Technology Agency
- JSPS
- Global COE Program (Integrative Life Science Based on the Study of Biosignaling Mechanisms)
- MEXT, Japan
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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.
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