A truncation allele in vascular endothelial growth factor c reveals distinct modes of signaling during lymphatic and vascular development
Identifieur interne : 003927 ( Main/Exploration ); précédent : 003926; suivant : 003928A truncation allele in vascular endothelial growth factor c reveals distinct modes of signaling during lymphatic and vascular development
Auteurs : Jacques A. Villefranc [États-Unis] ; Stefania Nicoli [États-Unis] ; Katie Bentley [Royaume-Uni] ; Michael Jeltsch [Finlande] ; Georgia Zarkada [Finlande] ; John C. Moore [États-Unis] ; Holger Gerhardt [Royaume-Uni] ; Kari Alitalo [Finlande] ; Nathan D. Lawson [États-Unis]Source :
- Development (Cambridge, England) [ 0950-1991 ] ; 2013.
Abstract
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
Url:
DOI: 10.1242/dev.084152
PubMed: 23462469
PubMed Central: 3596992
Affiliations:
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Villefranc</name><affiliation wicri:level="1"><nlm:aff id="A1"> Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, MA 01605, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea> Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, MA 01605</wicri:regionArea><wicri:noRegion>MA 01605</wicri:noRegion></affiliation></author><author><name sortKey="Nicoli, Stefania" sort="Nicoli, Stefania" uniqKey="Nicoli S" first="Stefania" last="Nicoli">Stefania Nicoli</name><affiliation wicri:level="1"><nlm:aff id="A1"> Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, MA 01605, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea> Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, MA 01605</wicri:regionArea><wicri:noRegion>MA 01605</wicri:noRegion></affiliation></author><author><name sortKey="Bentley, Katie" sort="Bentley, Katie" uniqKey="Bentley K" first="Katie" last="Bentley">Katie Bentley</name><affiliation wicri:level="1"><nlm:aff id="A2"> Cancer Research UK, London Research Institute, Lincoln’s Inn Fields, London WC2A 3LY, UK.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea> Cancer Research UK, London Research Institute, Lincoln’s Inn Fields, London WC2A 3LY</wicri:regionArea><wicri:noRegion>London WC2A 3LY</wicri:noRegion></affiliation></author><author><name sortKey="Jeltsch, Michael" sort="Jeltsch, Michael" uniqKey="Jeltsch M" first="Michael" last="Jeltsch">Michael Jeltsch</name><affiliation wicri:level="4"><nlm:aff id="A3"> Molecular Cancer Biology Program, Biomedicum Helsinki, Haartman Institute, University of Helsinki, Haartmaninkatu 8 (PO Box 63), FI-00014, Helsinki, Finland.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Finlande</country><wicri:regionArea> Molecular Cancer Biology Program, Biomedicum Helsinki, Haartman Institute, University of Helsinki, Haartmaninkatu 8 (PO Box 63), FI-00014, Helsinki</wicri:regionArea><orgName type="university">Université d'Helsinki</orgName><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName></affiliation></author><author><name sortKey="Zarkada, Georgia" sort="Zarkada, Georgia" uniqKey="Zarkada G" first="Georgia" last="Zarkada">Georgia Zarkada</name><affiliation wicri:level="4"><nlm:aff id="A3"> Molecular Cancer Biology Program, Biomedicum Helsinki, Haartman Institute, University of Helsinki, Haartmaninkatu 8 (PO Box 63), FI-00014, Helsinki, Finland.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Finlande</country><wicri:regionArea> Molecular Cancer Biology Program, Biomedicum Helsinki, Haartman Institute, University of Helsinki, Haartmaninkatu 8 (PO Box 63), FI-00014, Helsinki</wicri:regionArea><orgName type="university">Université d'Helsinki</orgName><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName></affiliation></author><author><name sortKey="Moore, John C" sort="Moore, John C" uniqKey="Moore J" first="John C." last="Moore">John C. Moore</name><affiliation wicri:level="1"><nlm:aff id="A1"> Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, MA 01605, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea> Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, MA 01605</wicri:regionArea><wicri:noRegion>MA 01605</wicri:noRegion></affiliation></author><author><name sortKey="Gerhardt, Holger" sort="Gerhardt, Holger" uniqKey="Gerhardt H" first="Holger" last="Gerhardt">Holger Gerhardt</name><affiliation wicri:level="1"><nlm:aff id="A2"> Cancer Research UK, London Research Institute, Lincoln’s Inn Fields, London WC2A 3LY, UK.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea> Cancer Research UK, London Research Institute, Lincoln’s Inn Fields, London WC2A 3LY</wicri:regionArea><wicri:noRegion>London WC2A 3LY</wicri:noRegion></affiliation></author><author><name sortKey="Alitalo, Kari" sort="Alitalo, Kari" uniqKey="Alitalo K" first="Kari" last="Alitalo">Kari Alitalo</name><affiliation wicri:level="4"><nlm:aff id="A3"> Molecular Cancer Biology Program, Biomedicum Helsinki, Haartman Institute, University of Helsinki, Haartmaninkatu 8 (PO Box 63), FI-00014, Helsinki, Finland.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Finlande</country><wicri:regionArea> Molecular Cancer Biology Program, Biomedicum Helsinki, Haartman Institute, University of Helsinki, Haartmaninkatu 8 (PO Box 63), FI-00014, Helsinki</wicri:regionArea><orgName type="university">Université d'Helsinki</orgName><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName><orgName type="university">Université d'Helsinki</orgName></affiliation></author><author><name sortKey="Lawson, Nathan D" sort="Lawson, Nathan D" uniqKey="Lawson N" first="Nathan D." last="Lawson">Nathan D. Lawson</name><affiliation wicri:level="1"><nlm:aff id="A1"> Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, MA 01605, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea> Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, MA 01605</wicri:regionArea><wicri:noRegion>MA 01605</wicri:noRegion></affiliation></author></analytic><series><title level="j">Development (Cambridge, England)</title><idno type="ISSN">0950-1991</idno><idno type="eISSN">1477-9129</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P3">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 <italic>vegfc</italic> that severely affects lymphatic development and leads to angiogenesis defects on sensitized genetic backgrounds. The <italic>um18</italic> mutation prematurely truncated Vegfc, blocking its secretion and paracrine activity but not its ability to activate its receptor Flt4. When expressed in endothelial cells, <italic>vegfc<sup>um18</sup></italic> could not rescue lymphatic defects in mutant embryos, but induced ectopic blood vessel branching. Furthermore, <italic>vegfc</italic>-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></div></front></TEI><affiliations><list><country><li>Finlande</li><li>Royaume-Uni</li><li>États-Unis</li></country><region><li>Uusimaa</li></region><settlement><li>Helsinki</li></settlement><orgName><li>Université d'Helsinki</li></orgName></list><tree><country name="États-Unis"><noRegion><name sortKey="Villefranc, Jacques A" sort="Villefranc, Jacques A" uniqKey="Villefranc J" first="Jacques A." last="Villefranc">Jacques A. Villefranc</name></noRegion><name sortKey="Lawson, Nathan D" sort="Lawson, Nathan D" uniqKey="Lawson N" first="Nathan D." last="Lawson">Nathan D. Lawson</name><name sortKey="Moore, John C" sort="Moore, John C" uniqKey="Moore J" first="John C." last="Moore">John C. Moore</name><name sortKey="Nicoli, Stefania" sort="Nicoli, Stefania" uniqKey="Nicoli S" first="Stefania" last="Nicoli">Stefania Nicoli</name></country><country name="Royaume-Uni"><noRegion><name sortKey="Bentley, Katie" sort="Bentley, Katie" uniqKey="Bentley K" first="Katie" last="Bentley">Katie Bentley</name></noRegion><name sortKey="Gerhardt, Holger" sort="Gerhardt, Holger" uniqKey="Gerhardt H" first="Holger" last="Gerhardt">Holger Gerhardt</name></country><country name="Finlande"><region name="Uusimaa"><name sortKey="Jeltsch, Michael" sort="Jeltsch, Michael" uniqKey="Jeltsch M" first="Michael" last="Jeltsch">Michael Jeltsch</name></region><name sortKey="Alitalo, Kari" sort="Alitalo, Kari" uniqKey="Alitalo K" first="Kari" last="Alitalo">Kari Alitalo</name><name sortKey="Zarkada, Georgia" sort="Zarkada, Georgia" uniqKey="Zarkada G" first="Georgia" last="Zarkada">Georgia Zarkada</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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