Context-dependent functional divergence of the notch ligands DLL1 and DLL4 In Vivo
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10451/49576 |
Resumo: | Copyright: © 2015 Preuße et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited |
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Context-dependent functional divergence of the notch ligands DLL1 and DLL4 In VivoCopyright: © 2015 Preuße et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedNotch signalling is a fundamental pathway that shapes the developing embryo and sustains adult tissues by direct communication between ligand and receptor molecules on adjacent cells. Among the ligands are two Delta paralogues, DLL1 and DLL4, that are conserved in mammals and share a similar structure and sequence. They activate the Notch receptor partly in overlapping expression domains where they fulfil redundant functions in some processes (e.g. maintenance of the crypt cell progenitor pool). In other processes, however, they appear to act differently (e.g. maintenance of foetal arterial identity) raising the questions of how similar DLL1 and DLL4 really are and which mechanism causes the apparent context-dependent divergence. By analysing mice that conditionally overexpress DLL1 or DLL4 from the same genomic locus (Hprt) and mice that express DLL4 instead of DLL1 from the endogenous Dll1 locus (Dll1Dll4ki), we found functional differences that are tissue-specific: while DLL1 and DLL4 act redundantly during the maintenance of retinal progenitors, their function varies in the presomitic mesoderm (PSM) where somites form in a Notch-dependent process. In the anterior PSM, every cell expresses both Notch receptors and ligands, and DLL1 is the only activator of Notch while DLL4 is not endogenously expressed. Transgenic DLL4 cannot replace DLL1 during somitogenesis and in heterozygous Dll1Dll4ki/+ mice, the Dll1Dll4ki allele causes a dominant segmentation phenotype. Testing several aspects of the complex Notch signalling system in vitro, we found that both ligands have a similar trans-activation potential but that only DLL4 is an efficient cis-inhibitor of Notch signalling, causing a reduced net activation of Notch. These differential cis-inhibitory properties are likely to contribute to the functional divergence of DLL1 and DLL4.Funding: This work was supported by grant GO 449/13-1 from the Deutsche Forschungsgemeinschaft (http://www.dfg.de) to AG, by funding of the Cluster of Excellence “From Regenerative Biology to Reconstructive Therapy” to AG (http://www.mh-hannover.de/rebirth.html) and by grant PTDC/SAU-BID/121846/2010 of the Fundação para a Ciência e a Tecnologia (http://www.fct.pt/index.phtml.en) to DH.PLOSRepositório da Universidade de LisboaPreuße, KristinaTveriakhina, LenaSchuster-Gossler, KarinGaspar, CláudiaRosa, Alexandra IsabelHenrique, DomingosGossler, AchimStauber, Michael2021-09-22T16:57:35Z20152015-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/49576engPLoS Genet. 2015 Jun 26;11(6):e10053281553-739010.1371/journal.pgen.10053281553-7404info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:53:29Zoai:repositorio.ul.pt:10451/49576Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:01:12.430428Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Context-dependent functional divergence of the notch ligands DLL1 and DLL4 In Vivo |
title |
Context-dependent functional divergence of the notch ligands DLL1 and DLL4 In Vivo |
spellingShingle |
Context-dependent functional divergence of the notch ligands DLL1 and DLL4 In Vivo Preuße, Kristina |
title_short |
Context-dependent functional divergence of the notch ligands DLL1 and DLL4 In Vivo |
title_full |
Context-dependent functional divergence of the notch ligands DLL1 and DLL4 In Vivo |
title_fullStr |
Context-dependent functional divergence of the notch ligands DLL1 and DLL4 In Vivo |
title_full_unstemmed |
Context-dependent functional divergence of the notch ligands DLL1 and DLL4 In Vivo |
title_sort |
Context-dependent functional divergence of the notch ligands DLL1 and DLL4 In Vivo |
author |
Preuße, Kristina |
author_facet |
Preuße, Kristina Tveriakhina, Lena Schuster-Gossler, Karin Gaspar, Cláudia Rosa, Alexandra Isabel Henrique, Domingos Gossler, Achim Stauber, Michael |
author_role |
author |
author2 |
Tveriakhina, Lena Schuster-Gossler, Karin Gaspar, Cláudia Rosa, Alexandra Isabel Henrique, Domingos Gossler, Achim Stauber, Michael |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
dc.contributor.author.fl_str_mv |
Preuße, Kristina Tveriakhina, Lena Schuster-Gossler, Karin Gaspar, Cláudia Rosa, Alexandra Isabel Henrique, Domingos Gossler, Achim Stauber, Michael |
description |
Copyright: © 2015 Preuße et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015 2015-01-01T00:00:00Z 2021-09-22T16:57:35Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10451/49576 |
url |
http://hdl.handle.net/10451/49576 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
PLoS Genet. 2015 Jun 26;11(6):e1005328 1553-7390 10.1371/journal.pgen.1005328 1553-7404 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
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application/pdf |
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PLOS |
publisher.none.fl_str_mv |
PLOS |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799134560755122176 |