Context-dependent functional divergence of the notch ligands DLL1 and DLL4 In Vivo

Detalhes bibliográficos
Autor(a) principal: Preuße, Kristina
Data de Publicação: 2015
Outros Autores: Tveriakhina, Lena, Schuster-Gossler, Karin, Gaspar, Cláudia, Rosa, Alexandra Isabel, Henrique, Domingos, Gossler, Achim, Stauber, Michael
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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spelling 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
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv PLOS
publisher.none.fl_str_mv PLOS
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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