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Heterogeneity in VEGFR3 levels drives lymphatic vessel hyperplasia through cell-autonomous and non-cell-autonomous mechanisms

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Heterogeneity in VEGFR3 levels drives lymphatic vessel hyperplasia through cell-autonomous and non-cell-autonomous mechanisms. / Zhang, Yan; Ulvmar, Maria H; Stanczuk, Lukas; Martinez-Corral, Ines; Frye, Maike; Alitalo, Kari; Mäkinen, Taija.

in: NAT COMMUN, Jahrgang 9, Nr. 1, 03.04.2018, S. 1296.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Zhang, Y, Ulvmar, MH, Stanczuk, L, Martinez-Corral, I, Frye, M, Alitalo, K & Mäkinen, T 2018, 'Heterogeneity in VEGFR3 levels drives lymphatic vessel hyperplasia through cell-autonomous and non-cell-autonomous mechanisms', NAT COMMUN, Jg. 9, Nr. 1, S. 1296. https://doi.org/10.1038/s41467-018-03692-0

APA

Zhang, Y., Ulvmar, M. H., Stanczuk, L., Martinez-Corral, I., Frye, M., Alitalo, K., & Mäkinen, T. (2018). Heterogeneity in VEGFR3 levels drives lymphatic vessel hyperplasia through cell-autonomous and non-cell-autonomous mechanisms. NAT COMMUN, 9(1), 1296. https://doi.org/10.1038/s41467-018-03692-0

Vancouver

Zhang Y, Ulvmar MH, Stanczuk L, Martinez-Corral I, Frye M, Alitalo K et al. Heterogeneity in VEGFR3 levels drives lymphatic vessel hyperplasia through cell-autonomous and non-cell-autonomous mechanisms. NAT COMMUN. 2018 Apr 3;9(1):1296. https://doi.org/10.1038/s41467-018-03692-0

Bibtex

@article{31b707bbbe8344eba5f0cd83ca565cec,
title = "Heterogeneity in VEGFR3 levels drives lymphatic vessel hyperplasia through cell-autonomous and non-cell-autonomous mechanisms",
abstract = "Incomplete delivery to the target cells is an obstacle for successful gene therapy approaches. Here we show unexpected effects of incomplete targeting, by demonstrating how heterogeneous inhibition of a growth promoting signaling pathway promotes tissue hyperplasia. We studied the function of the lymphangiogenic VEGFR3 receptor during embryonic and post-natal development. Inducible genetic deletion of Vegfr3 in lymphatic endothelial cells (LECs) leads to selection of non-targeted VEGFR3+cells at vessel tips, indicating an indispensable cell-autonomous function in migrating tip cells. Although Vegfr3 deletion results in lymphatic hypoplasia in mouse embryos, incomplete deletion during post-natal development instead causes excessive lymphangiogenesis. Analysis of mosaically targeted endothelium shows that VEGFR3-LECs non-cell-autonomously drive abnormal vessel anastomosis and hyperplasia by inducing proliferation of non-targeted VEGFR3+LECs through cell-contact-dependent reduction of Notch signaling. Heterogeneity in VEGFR3 levels thus drives vessel hyperplasia, which has implications for the understanding of mechanisms of developmental and pathological tissue growth.",
keywords = "Journal Article",
author = "Yan Zhang and Ulvmar, {Maria H} and Lukas Stanczuk and Ines Martinez-Corral and Maike Frye and Kari Alitalo and Taija M{\"a}kinen",
year = "2018",
month = apr,
day = "3",
doi = "10.1038/s41467-018-03692-0",
language = "English",
volume = "9",
pages = "1296",
journal = "NAT COMMUN",
issn = "2041-1723",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - Heterogeneity in VEGFR3 levels drives lymphatic vessel hyperplasia through cell-autonomous and non-cell-autonomous mechanisms

AU - Zhang, Yan

AU - Ulvmar, Maria H

AU - Stanczuk, Lukas

AU - Martinez-Corral, Ines

AU - Frye, Maike

AU - Alitalo, Kari

AU - Mäkinen, Taija

PY - 2018/4/3

Y1 - 2018/4/3

N2 - Incomplete delivery to the target cells is an obstacle for successful gene therapy approaches. Here we show unexpected effects of incomplete targeting, by demonstrating how heterogeneous inhibition of a growth promoting signaling pathway promotes tissue hyperplasia. We studied the function of the lymphangiogenic VEGFR3 receptor during embryonic and post-natal development. Inducible genetic deletion of Vegfr3 in lymphatic endothelial cells (LECs) leads to selection of non-targeted VEGFR3+cells at vessel tips, indicating an indispensable cell-autonomous function in migrating tip cells. Although Vegfr3 deletion results in lymphatic hypoplasia in mouse embryos, incomplete deletion during post-natal development instead causes excessive lymphangiogenesis. Analysis of mosaically targeted endothelium shows that VEGFR3-LECs non-cell-autonomously drive abnormal vessel anastomosis and hyperplasia by inducing proliferation of non-targeted VEGFR3+LECs through cell-contact-dependent reduction of Notch signaling. Heterogeneity in VEGFR3 levels thus drives vessel hyperplasia, which has implications for the understanding of mechanisms of developmental and pathological tissue growth.

AB - Incomplete delivery to the target cells is an obstacle for successful gene therapy approaches. Here we show unexpected effects of incomplete targeting, by demonstrating how heterogeneous inhibition of a growth promoting signaling pathway promotes tissue hyperplasia. We studied the function of the lymphangiogenic VEGFR3 receptor during embryonic and post-natal development. Inducible genetic deletion of Vegfr3 in lymphatic endothelial cells (LECs) leads to selection of non-targeted VEGFR3+cells at vessel tips, indicating an indispensable cell-autonomous function in migrating tip cells. Although Vegfr3 deletion results in lymphatic hypoplasia in mouse embryos, incomplete deletion during post-natal development instead causes excessive lymphangiogenesis. Analysis of mosaically targeted endothelium shows that VEGFR3-LECs non-cell-autonomously drive abnormal vessel anastomosis and hyperplasia by inducing proliferation of non-targeted VEGFR3+LECs through cell-contact-dependent reduction of Notch signaling. Heterogeneity in VEGFR3 levels thus drives vessel hyperplasia, which has implications for the understanding of mechanisms of developmental and pathological tissue growth.

KW - Journal Article

U2 - 10.1038/s41467-018-03692-0

DO - 10.1038/s41467-018-03692-0

M3 - SCORING: Journal article

C2 - 29615616

VL - 9

SP - 1296

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

IS - 1

ER -