Show simple item record

dc.contributor.authorVillefranc, Jacques A.
dc.contributor.authorNicoli, Stefania
dc.contributor.authorBentley, Katie
dc.contributor.authorJeltsch, Michael
dc.contributor.authorZarkada, Georgia
dc.contributor.authorMoore, John C.
dc.contributor.authorGerhardt, Holger
dc.contributor.authorAlitalo, Kari
dc.contributor.authorLawson, Nathan D.
dc.date2022-08-11T08:08:19.000
dc.date.accessioned2022-08-23T15:51:12Z
dc.date.available2022-08-23T15:51:12Z
dc.date.issued2013-04-01
dc.date.submitted2013-07-02
dc.identifier.citation<p>Development. 2013 Apr;140(7):1497-506. doi: 10.1242/dev.084152. Epub 2013 Mar 5. <a href="http://dx.doi.org/10.1242/dev.084152">Link to article on publisher's site</a></p>
dc.identifier.issn0950-1991 (Linking)
dc.identifier.doi10.1242/dev.084152
dc.identifier.pmid23462469
dc.identifier.urihttp://hdl.handle.net/20.500.14038/28842
dc.description.abstractVascular endothelial growth factor C (Vegfc) is a secreted protein that guides lymphatic development in vertebrate embryos. However, its role during developmental angiogenesis is not well characterized. Here, we identify a mutation in zebrafish vegfc that severely affects lymphatic development and leads to angiogenesis defects on sensitized genetic backgrounds. The um18 mutation prematurely truncated Vegfc, blocking its secretion and paracrine activity but not its ability to activate its receptor Flt4. When expressed in endothelial cells, vegfc(um18) could not rescue lymphatic defects in mutant embryos, but induced ectopic blood vessel branching. Furthermore, vegfc-deficient endothelial cells did not efficiently contribute to tip cell positions in developing sprouts. Computational modeling together with assessment of endothelial cell dynamics by time-lapse analysis suggested that an autocrine Vegfc/Flt4 loop plays an important role in migratory persistence and filopodia stability during sprouting. Our results suggest that Vegfc acts in two distinct modes during development: as a paracrine factor secreted from arteries to guide closely associated lymphatic vasculature and as an autocrine factor to drive migratory persistence during angiogenesis.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=23462469&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rightsPublisher PDF posted as allowed by the publisher's author rights policy at http://dev.biologists.org/site/misc/rights_permissions.xhtml#author
dc.subjectAlleles
dc.subjectAnimals
dc.subjectAnimals, Genetically Modified
dc.subjectAutocrine Communication
dc.subjectBlood Vessels
dc.subjectCell Movement
dc.subjectCodon, Nonsense
dc.subjectEmbryo, Nonmammalian
dc.subjectFemale
dc.subjectLymphatic System
dc.subjectMice
dc.subjectMice, Knockout
dc.subjectNeovascularization, Physiologic
dc.subjectParacrine Communication
dc.subjectProtein Isoforms
dc.subjectSignal Transduction
dc.subjectVascular Endothelial Growth Factor C
dc.subjectZebrafish
dc.subjectZebrafish Proteins
dc.subjectVegfc
dc.subjectAngiogenesis
dc.subjectLymphatic
dc.subjectZebrafish
dc.subjectCellular and Molecular Physiology
dc.subjectDevelopmental Biology
dc.subjectEmbryonic Structures
dc.subjectGenetic Phenomena
dc.subjectHemic and Immune Systems
dc.subjectInvestigative Techniques
dc.titleA truncation allele in vascular endothelial growth factor c reveals distinct modes of signaling during lymphatic and vascular development
dc.typeJournal Article
dc.source.journaltitleDevelopment (Cambridge, England)
dc.source.volume140
dc.source.issue7
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1107&amp;context=faculty_pubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/108
dc.identifier.contextkey4276324
refterms.dateFOA2022-08-23T15:51:13Z
html.description.abstract<p>Vascular endothelial growth factor C (Vegfc) is a secreted protein that guides lymphatic development in vertebrate embryos. However, its role during developmental angiogenesis is not well characterized. Here, we identify a mutation in zebrafish vegfc that severely affects lymphatic development and leads to angiogenesis defects on sensitized genetic backgrounds. The um18 mutation prematurely truncated Vegfc, blocking its secretion and paracrine activity but not its ability to activate its receptor Flt4. When expressed in endothelial cells, vegfc(um18) could not rescue lymphatic defects in mutant embryos, but induced ectopic blood vessel branching. Furthermore, vegfc-deficient endothelial cells did not efficiently contribute to tip cell positions in developing sprouts. Computational modeling together with assessment of endothelial cell dynamics by time-lapse analysis suggested that an autocrine Vegfc/Flt4 loop plays an important role in migratory persistence and filopodia stability during sprouting. Our results suggest that Vegfc acts in two distinct modes during development: as a paracrine factor secreted from arteries to guide closely associated lymphatic vasculature and as an autocrine factor to drive migratory persistence during angiogenesis.</p>
dc.identifier.submissionpathfaculty_pubs/108
dc.contributor.departmentProgram in Gene Function and Expression
dc.source.pages1497-506


Files in this item

Thumbnail
Name:
Development_Villefranc_1497.fu ...
Size:
2.443Mb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record