Logo do repositório
 
Publicação

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

2015Artigo científico Acesso aberto
Ver registo simples
dc.contributor.authorPreuße, Kristina
dc.contributor.authorTveriakhina, Lena
dc.contributor.authorSchuster-Gossler, Karin
dc.contributor.authorGaspar, Cláudia
dc.contributor.authorRosa, Alexandra Isabel
dc.contributor.authorHenrique, Domingos
dc.contributor.authorGossler, Achim
dc.contributor.authorStauber, Michael
dc.date.accessioned2021-09-22T16:57:35Z
dc.date.available2021-09-22T16:57:35Z
dc.date.issued2015
dc.descriptionCopyright: © 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 creditedpt_PT
dc.description.abstractNotch 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.pt_PT
dc.description.sponsorshipFunding: 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.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationPLoS Genet. 2015 Jun 26;11(6):e1005328pt_PT
dc.identifier.doi10.1371/journal.pgen.1005328pt_PT
dc.identifier.eissn1553-7404
dc.identifier.issn1553-7390
dc.identifier.urihttp://hdl.handle.net/10451/49576
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherPLOSpt_PT
dc.relationThe V2 domain of the spinal cord as a model to study neuronal fate decisions
dc.relation.publisherversionhttps://journals.plos.org/plosgenetics/pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.titleContext-dependent functional divergence of the notch ligands DLL1 and DLL4 In Vivopt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardNumberPTDC/SAU-BID/121846/2010
oaire.awardTitleThe V2 domain of the spinal cord as a model to study neuronal fate decisions
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FSAU-BID%2F121846%2F2010/PT
oaire.citation.issue6pt_PT
oaire.citation.titlePLOS Geneticspt_PT
oaire.citation.volume11pt_PT
oaire.fundingStream3599-PPCDT
person.familyNameGaspar
person.familyNameRosa
person.familyNamePinto Henrique
person.givenNameClaudia
person.givenNameAlexandra
person.givenNameDomingos Manuel
person.identifierhttps://scholar.google.com/citations?user=GoogleScholarID=en&authuser=1&user=K8mZSYQAAAAJ
person.identifier.ciencia-idC111-5D28-EC65
person.identifier.orcid0000-0003-1051-0998
person.identifier.orcid0000-0001-6184-9911
person.identifier.orcid0000-0001-8869-1894
person.identifier.ridI-6402-2013
person.identifier.ridJ-8659-2013
person.identifier.scopus-author-id36991639300
person.identifier.scopus-author-id23019749900
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicationa4de13f4-2209-4682-aee7-975bfff01d31
relation.isAuthorOfPublicationd5497c21-fd9b-41d8-80db-3791f4cdf6c3
relation.isAuthorOfPublicationd66f1f29-0686-4c76-97b0-4f350eafdcb8
relation.isAuthorOfPublication.latestForDiscoveryd5497c21-fd9b-41d8-80db-3791f4cdf6c3
relation.isProjectOfPublication6e861767-15cb-46c7-b2cd-f7698fafb6c1
relation.isProjectOfPublication.latestForDiscovery6e861767-15cb-46c7-b2cd-f7698fafb6c1

Ficheiros

Principais
A mostrar 1 - 1 de 1
Miniatura
Nome:
DLL1_DLL4.pdf
Tamanho:
16.08 MB
Formato:
Adobe Portable Document Format
Ver/Abrir

Coleções

IMM - Artigos em Revistas Internacionais
FM - Artigos em Revistas Internacionais