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Title: Oscillatory control of Delta-like1 in cell interactions regulates dynamic gene expression and tissue morphogenesis
Authors: Shimojo, Hiromi  kyouindb  KAKEN_id
Isomura, Akihiro  kyouindb  KAKEN_id
Ohtsuka, Toshiyuki  kyouindb  KAKEN_id
Kori, Hiroshi
Miyachi, Hitoshi
Kageyama, Ryoichiro  kyouindb  KAKEN_id  orcid (unconfirmed)
Author's alias: 下條, 博美
大塚, 俊之
影山, 龍一郎
Keywords: Dll1
Neural development
Somite segmentation
Time-lapse imaging
Issue Date: 1-Jan-2016
Publisher: Cold Spring Harbor Laboratory Press
Journal title: Genes & Development
Volume: 30
Start page: 102
End page: 116
Abstract: Notch signaling regulates tissue morphogenesis through cell–cell interactions. The Notch effectors Hes1 and Hes7 are expressed in an oscillatory manner and regulate developmental processes such as neurogenesis and somitogenesis, respectively. Expression of the mRNA for the mouse Notch ligand Delta-like1 (Dll1) is also oscillatory. However, the dynamics of Dll1 protein expression are controversial, and their functional significance is unknown. Here, we developed a live-imaging system and found that Dll1 protein expression oscillated in neural progenitors and presomitic mesoderm cells. Notably, when Dll1 expression was accelerated or delayed by shortening or elongating the Dll1 gene, Dll1 oscillations became severely dampened or quenched at intermediate levels, as modeled mathematically. Under this condition, Hes1 and Hes7 oscillations were also dampened. In the presomitic mesoderm, steady Dll1 expression led to severe fusion of somites and their derivatives, such as vertebrae and ribs. In the developing brain, steady Dll1 expression inhibited proliferation of neural progenitors and accelerated neurogenesis, whereas optogenetic induction of Dll1 oscillation efficiently maintained neural progenitors. These results indicate that the appropriate timing of Dll1 expression is critical for the oscillatory networks and suggest the functional significance of oscillatory cell–cell interactions in tissue morphogenesis.
Rights: ©2016 Shimojo et al. This article, published in Genes & Development, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at
DOI(Published Version): 10.1101/gad.270785.115
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