Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Shimojo, Hiromi, Isomura, Akihiro, Ohtsuka, Toshiyuki, Kori, Hiroshi, Miyachi, Hitoshi, Kageyama, Ryoichiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2016
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
_version_ 1782408565451915264
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
work_keys_str_mv AT shimojohiromi oscillatorycontrolofdeltalike1incellinteractionsregulatesdynamicgeneexpressionandtissuemorphogenesis
AT isomuraakihiro oscillatorycontrolofdeltalike1incellinteractionsregulatesdynamicgeneexpressionandtissuemorphogenesis
AT ohtsukatoshiyuki oscillatorycontrolofdeltalike1incellinteractionsregulatesdynamicgeneexpressionandtissuemorphogenesis
AT korihiroshi oscillatorycontrolofdeltalike1incellinteractionsregulatesdynamicgeneexpressionandtissuemorphogenesis
AT miyachihitoshi oscillatorycontrolofdeltalike1incellinteractionsregulatesdynamicgeneexpressionandtissuemorphogenesis
AT kageyamaryoichiro oscillatorycontrolofdeltalike1incellinteractionsregulatesdynamicgeneexpressionandtissuemorphogenesis