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Myeloid Wnt ligands are required for normal development of dermal lymphatic vasculature

Identifieur interne : 004431 ( Pmc/Curation ); précédent : 004430; suivant : 004432

Myeloid Wnt ligands are required for normal development of dermal lymphatic vasculature

Auteurs : Ajit Muley [États-Unis] ; Yoshi Odaka [États-Unis] ; Ian P. Lewkowich [États-Unis] ; Shruti Vemaraju [États-Unis] ; Terry P. Yamaguchi [États-Unis] ; Carrie Shawber [États-Unis] ; Belinda H. Dickie [États-Unis] ; Richard A. Lang [États-Unis]

Source :

RBID : PMC:5573294

Abstract

Resident tissue myeloid cells play a role in many aspects of physiology including development of the vascular systems. In the blood vasculature, myeloid cells use VEGFC to promote angiogenesis and can use Wnt ligands to control vascular branching and to promote vascular regression. Here we show that myeloid cells also regulate development of the dermal lymphatic vasculature using Wnt ligands. Using myeloid-specific deletion of the WNT transporter Wntless we show that myeloid Wnt ligands are active at two distinct stages of development of the dermal lymphatics. As lymphatic progenitors are emigrating from the cardinal vein and intersomitic vessels, myeloid Wnt ligands regulate both their numbers and migration distance. Later in lymphatic development, myeloid Wnt ligands regulate proliferation of lymphatic endothelial cells (LEC) and thus control lymphatic vessel caliber. Myeloid-specific deletion of WNT co-receptor Lrp5 or Wnt5a gain-of-function also produce elevated caliber in dermal lymphatic capillaries. These data thus suggest that myeloid cells produce Wnt ligands to regulate lymphatic development and use Wnt pathway co-receptors to regulate the balance of Wnt ligand activity during the macrophage-LEC interaction.


Url:
DOI: 10.1371/journal.pone.0181549
PubMed: 28846685
PubMed Central: 5573294

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PMC:5573294

Le document en format XML

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<p>Resident tissue myeloid cells play a role in many aspects of physiology including development of the vascular systems. In the blood vasculature, myeloid cells use VEGFC to promote angiogenesis and can use Wnt ligands to control vascular branching and to promote vascular regression. Here we show that myeloid cells also regulate development of the dermal lymphatic vasculature using Wnt ligands. Using myeloid-specific deletion of the WNT transporter
<italic>Wntless</italic>
we show that myeloid Wnt ligands are active at two distinct stages of development of the dermal lymphatics. As lymphatic progenitors are emigrating from the cardinal vein and intersomitic vessels, myeloid Wnt ligands regulate both their numbers and migration distance. Later in lymphatic development, myeloid Wnt ligands regulate proliferation of lymphatic endothelial cells (LEC) and thus control lymphatic vessel caliber. Myeloid-specific deletion of WNT co-receptor
<italic>Lrp5</italic>
or
<italic>Wnt5a</italic>
gain-of-function also produce elevated caliber in dermal lymphatic capillaries. These data thus suggest that myeloid cells produce Wnt ligands to regulate lymphatic development and use Wnt pathway co-receptors to regulate the balance of Wnt ligand activity during the macrophage-LEC interaction.</p>
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<article-id pub-id-type="pmc">5573294</article-id>
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<subj-group>
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<subj-group>
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<subj-group>
<subject>Veins</subject>
<subj-group>
<subject>Jugular Vein</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3">
<subject>Medicine and Health Sciences</subject>
<subj-group>
<subject>Anatomy</subject>
<subj-group>
<subject>Cardiovascular Anatomy</subject>
<subj-group>
<subject>Blood Vessels</subject>
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<subject>Jugular Vein</subject>
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<article-title>Myeloid Wnt ligands are required for normal development of dermal lymphatic vasculature</article-title>
<alt-title alt-title-type="running-head">Wnt ligands from myeloid cells regulate normal lymphatic development in dermal tissue</alt-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Muley</surname>
<given-names>Ajit</given-names>
</name>
<role content-type="http://credit.casrai.org/">Conceptualization</role>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Formal analysis</role>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Methodology</role>
<role content-type="http://credit.casrai.org/">Writing – original draft</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff001">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Odaka</surname>
<given-names>Yoshi</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Formal analysis</role>
<role content-type="http://credit.casrai.org/">Investigation</role>
<xref ref-type="aff" rid="aff002">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Lewkowich</surname>
<given-names>Ian P.</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Investigation</role>
<xref ref-type="aff" rid="aff003">
<sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Vemaraju</surname>
<given-names>Shruti</given-names>
</name>
<role content-type="http://credit.casrai.org/">Formal analysis</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff002">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Yamaguchi</surname>
<given-names>Terry P.</given-names>
</name>
<role content-type="http://credit.casrai.org/">Resources</role>
<xref ref-type="aff" rid="aff004">
<sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Shawber</surname>
<given-names>Carrie</given-names>
</name>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff001">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Dickie</surname>
<given-names>Belinda H.</given-names>
</name>
<role content-type="http://credit.casrai.org/">Conceptualization</role>
<role content-type="http://credit.casrai.org/">Methodology</role>
<role content-type="http://credit.casrai.org/">Writing – original draft</role>
<xref ref-type="aff" rid="aff005">
<sup>5</sup>
</xref>
<xref ref-type="corresp" rid="cor001">*</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0002-5212-254X</contrib-id>
<name>
<surname>Lang</surname>
<given-names>Richard A.</given-names>
</name>
<role content-type="http://credit.casrai.org/">Conceptualization</role>
<role content-type="http://credit.casrai.org/">Funding acquisition</role>
<role content-type="http://credit.casrai.org/">Methodology</role>
<role content-type="http://credit.casrai.org/">Writing – original draft</role>
<role content-type="http://credit.casrai.org/">Writing – review & editing</role>
<xref ref-type="aff" rid="aff002">
<sup>2</sup>
</xref>
<xref ref-type="aff" rid="aff006">
<sup>6</sup>
</xref>
<xref ref-type="aff" rid="aff007">
<sup>7</sup>
</xref>
<xref ref-type="aff" rid="aff008">
<sup>8</sup>
</xref>
<xref ref-type="aff" rid="aff009">
<sup>9</sup>
</xref>
<xref ref-type="corresp" rid="cor001">*</xref>
</contrib>
</contrib-group>
<aff id="aff001">
<label>1</label>
<addr-line>Department of OB-GYN, Columbia University Medical Center, Columbia University, New York City, New York, United States of America</addr-line>
</aff>
<aff id="aff002">
<label>2</label>
<addr-line>Visual Systems Group, Division of Pediatric Ophthalmology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States of America</addr-line>
</aff>
<aff id="aff003">
<label>3</label>
<addr-line>Division of Immunobiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States of America</addr-line>
</aff>
<aff id="aff004">
<label>4</label>
<addr-line>Cancer and Developmental Biology Laboratory, National Cancer Institute, Frederick, Maryland, United States of America</addr-line>
</aff>
<aff id="aff005">
<label>5</label>
<addr-line>Department of Surgery, Boston Children's Hospital, Boston, Massachusetts, United States of America</addr-line>
</aff>
<aff id="aff006">
<label>6</label>
<addr-line>Center for Chronobiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States of America</addr-line>
</aff>
<aff id="aff007">
<label>7</label>
<addr-line>Abrahamson Pediatric Eye Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States of America</addr-line>
</aff>
<aff id="aff008">
<label>8</label>
<addr-line>Division of Developmental Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States of America</addr-line>
</aff>
<aff id="aff009">
<label>9</label>
<addr-line>Department of Ophthalmology, College of Medicine, University of Cincinnati, Cincinnati, Ohio, United States of America</addr-line>
</aff>
<contrib-group>
<contrib contrib-type="editor">
<name>
<surname>Luttun</surname>
<given-names>Aernout</given-names>
</name>
<role>Editor</role>
<xref ref-type="aff" rid="edit1"></xref>
</contrib>
</contrib-group>
<aff id="edit1">
<addr-line>Katholieke Universiteit Leuven, BELGIUM</addr-line>
</aff>
<author-notes>
<fn fn-type="COI-statement" id="coi001">
<p>
<bold>Competing Interests: </bold>
The authors have declared that no competing interests exist.</p>
</fn>
<corresp id="cor001">* E-mail:
<email>Richard.Lang@cchmc.org</email>
(RAL);
<email>Belinda.HsiDickie@childrens.harvard.edu</email>
(BHD)</corresp>
</author-notes>
<pub-date pub-type="epub">
<day>28</day>
<month>8</month>
<year>2017</year>
</pub-date>
<pub-date pub-type="collection">
<year>2017</year>
</pub-date>
<volume>12</volume>
<issue>8</issue>
<elocation-id>e0181549</elocation-id>
<history>
<date date-type="received">
<day>9</day>
<month>3</month>
<year>2017</year>
</date>
<date date-type="accepted">
<day>3</day>
<month>7</month>
<year>2017</year>
</date>
</history>
<permissions>
<license xlink:href="https://creativecommons.org/publicdomain/zero/1.0/">
<license-p>This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the
<ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/publicdomain/zero/1.0/">Creative Commons CC0</ext-link>
public domain dedication.</license-p>
</license>
</permissions>
<self-uri content-type="pdf" xlink:href="pone.0181549.pdf"></self-uri>
<abstract>
<p>Resident tissue myeloid cells play a role in many aspects of physiology including development of the vascular systems. In the blood vasculature, myeloid cells use VEGFC to promote angiogenesis and can use Wnt ligands to control vascular branching and to promote vascular regression. Here we show that myeloid cells also regulate development of the dermal lymphatic vasculature using Wnt ligands. Using myeloid-specific deletion of the WNT transporter
<italic>Wntless</italic>
we show that myeloid Wnt ligands are active at two distinct stages of development of the dermal lymphatics. As lymphatic progenitors are emigrating from the cardinal vein and intersomitic vessels, myeloid Wnt ligands regulate both their numbers and migration distance. Later in lymphatic development, myeloid Wnt ligands regulate proliferation of lymphatic endothelial cells (LEC) and thus control lymphatic vessel caliber. Myeloid-specific deletion of WNT co-receptor
<italic>Lrp5</italic>
or
<italic>Wnt5a</italic>
gain-of-function also produce elevated caliber in dermal lymphatic capillaries. These data thus suggest that myeloid cells produce Wnt ligands to regulate lymphatic development and use Wnt pathway co-receptors to regulate the balance of Wnt ligand activity during the macrophage-LEC interaction.</p>
</abstract>
<funding-group>
<award-group id="award001">
<funding-source>
<institution-wrap>
<institution-id institution-id-type="funder-id">http://dx.doi.org/10.13039/100000002</institution-id>
<institution>National Institutes of Health</institution>
</institution-wrap>
</funding-source>
<award-id>R01 EY021636</award-id>
<principal-award-recipient>
<contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0002-5212-254X</contrib-id>
<name>
<surname>Lang</surname>
<given-names>Richard A.</given-names>
</name>
</principal-award-recipient>
</award-group>
<award-group id="award002">
<funding-source>
<institution>CCHMC</institution>
</funding-source>
<award-id>Institutional Startup Funds</award-id>
<principal-award-recipient>
<name>
<surname>Dickie</surname>
<given-names>Belinda H.</given-names>
</name>
</principal-award-recipient>
</award-group>
<funding-statement>This work was supported by R01 EY021636. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement>
</funding-group>
<counts>
<fig-count count="7"></fig-count>
<table-count count="0"></table-count>
<page-count count="19"></page-count>
</counts>
<custom-meta-group>
<custom-meta id="data-availability">
<meta-name>Data Availability</meta-name>
<meta-value>All relevant data are within the paper and its Supporting Information files.</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
<notes>
<title>Data Availability</title>
<p>All relevant data are within the paper and its Supporting Information files.</p>
</notes>
</front>
</pmc>
</record>

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