Selection of differentiating cells by different levels of delta-like 1 among neural precursor cells in the developing mouse 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.
Kawaguchi
Daichi
D
Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Yoshimatsu
Takeshi
T
Hozumi
Katsuto
K
Gotoh
Yukiko
Y
D000818:Animals; D019521:Body Patterning; D002135:Calcium-Binding Proteins; D002450:Cell Communication; D002454:Cell Differentiation; D019070:Cell Lineage; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D019579:Neocortex / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D013687:Telencephalon / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism
D002135:Calcium-Binding Proteins; C512925:Dlk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D051881:Receptor, Notch1