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Oscillatory control of Delta-like1 in cell interactions regulates dynamic gene expression and tissue morphogenesis
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-l...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4701973/ https://www.ncbi.nlm.nih.gov/pubmed/26728556 http://dx.doi.org/10.1101/gad.270785.115 |
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author | Shimojo, Hiromi Isomura, Akihiro Ohtsuka, Toshiyuki Kori, Hiroshi Miyachi, Hitoshi Kageyama, Ryoichiro |
author_facet | Shimojo, Hiromi Isomura, Akihiro Ohtsuka, Toshiyuki Kori, Hiroshi Miyachi, Hitoshi Kageyama, Ryoichiro |
author_sort | Shimojo, Hiromi |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4701973 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-47019732016-01-11 Oscillatory control of Delta-like1 in cell interactions regulates dynamic gene expression and tissue morphogenesis Shimojo, Hiromi Isomura, Akihiro Ohtsuka, Toshiyuki Kori, Hiroshi Miyachi, Hitoshi Kageyama, Ryoichiro Genes Dev Research Paper 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. Cold Spring Harbor Laboratory Press 2016-01-01 /pmc/articles/PMC4701973/ /pubmed/26728556 http://dx.doi.org/10.1101/gad.270785.115 Text en © 2016 Shimojo et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article, published in Genes & Development, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/. |
spellingShingle | Research Paper Shimojo, Hiromi Isomura, Akihiro Ohtsuka, Toshiyuki Kori, Hiroshi Miyachi, Hitoshi Kageyama, Ryoichiro Oscillatory control of Delta-like1 in cell interactions regulates dynamic gene expression and tissue morphogenesis |
title | Oscillatory control of Delta-like1 in cell interactions regulates dynamic gene expression and tissue morphogenesis |
title_full | Oscillatory control of Delta-like1 in cell interactions regulates dynamic gene expression and tissue morphogenesis |
title_fullStr | Oscillatory control of Delta-like1 in cell interactions regulates dynamic gene expression and tissue morphogenesis |
title_full_unstemmed | Oscillatory control of Delta-like1 in cell interactions regulates dynamic gene expression and tissue morphogenesis |
title_short | Oscillatory control of Delta-like1 in cell interactions regulates dynamic gene expression and tissue morphogenesis |
title_sort | oscillatory control of delta-like1 in cell interactions regulates dynamic gene expression and tissue morphogenesis |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4701973/ https://www.ncbi.nlm.nih.gov/pubmed/26728556 http://dx.doi.org/10.1101/gad.270785.115 |
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