Prox1 Induces Lymphatic Endothelial Differentiation via Integrin α9 and Other Signaling Cascades
Identifieur interne : 003A97 ( Pmc/Checkpoint ); précédent : 003A96; suivant : 003A98Prox1 Induces Lymphatic Endothelial Differentiation via Integrin α9 and Other Signaling Cascades
Auteurs : Koichi Mishima [Japon] ; Tetsuro Watabe ; Akira Saito ; Yasuhiro Yoshimatsu ; Natsuko Imaizumi ; Shinji Masui [Japon] ; Masanori Hirashima [Japon] ; Tohru Morisada [Japon] ; Yuichi Oike [Japon] ; Makoto Araie [Japon] ; Hitoshi Niwa [Japon] ; Hajime Kubo [Japon] ; Toshio Suda [Japon] ; Kohei Miyazono [Japon]Source :
- Molecular Biology of the Cell [ 1059-1524 ] ; 2007.
Abstract
During embryonic lymphatic development, a homeobox transcription factor Prox1 plays important roles in sprouting and migration of a subpopulation of blood vessel endothelial cells (BECs) toward VEGF-C–expressing cells. However, effects of Prox1 on endothelial cellular behavior remain to be elucidated. Here, we show that Prox1, via induction of integrin α9 expression, inhibits sheet formation and stimulates motility of endothelial cells. Prox1-expressing BECs preferentially migrated toward VEGF-C via up-regulation of the expression of integrin α9 and VEGF receptor 3 (VEGFR3). In mouse embryos, expression of VEGFR3 and integrin α9 is increased in Prox1-expressing lymphatic endothelial cells (LECs) compared with BECs. Knockdown of Prox1 expression in human LECs led to decrease in the expression of integrin α9 and VEGFR3, resulting in the decreased chemotaxes toward VEGF-C. These findings suggest that Prox1 plays important roles in conferring and maintaining the characteristics of LECs by modulating multiple signaling cascades and that integrin α9 may function as a key regulator of lymphangiogenesis acting downstream of Prox1.
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DOI: 10.1091/mbc.E06-09-0780
PubMed: 17287396
PubMed Central: 1838981
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Prox1 Induces Lymphatic Endothelial Differentiation via Integrin α9 and Other Signaling Cascades<xref ref-type="fn" rid="FN1"><sup><inline-graphic xlink:href="dbox.jpg" mimetype="image"></inline-graphic><inline-graphic xlink:href="vbox.jpg" mimetype="image"></inline-graphic></sup></xref></title><author><name sortKey="Mishima, Koichi" sort="Mishima, Koichi" uniqKey="Mishima K" first="Koichi" last="Mishima">Koichi Mishima</name><affiliation><nlm:aff id="aff1">Departments of *Molecular Pathology and</nlm:aff></affiliation><affiliation wicri:level="4"><nlm:aff id="aff2">Ophthalmology, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan;</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Ophthalmology, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region><settlement type="city">Tokyo</settlement></placeName><orgName type="university">Université de Tokyo</orgName></affiliation></author><author><name sortKey="Watabe, Tetsuro" sort="Watabe, Tetsuro" uniqKey="Watabe T" first="Tetsuro" last="Watabe">Tetsuro Watabe</name><affiliation><nlm:aff id="aff1">Departments of *Molecular Pathology and</nlm:aff></affiliation></author><author><name sortKey="Saito, Akira" sort="Saito, Akira" uniqKey="Saito A" first="Akira" last="Saito">Akira Saito</name><affiliation><nlm:aff id="aff1">Departments of *Molecular Pathology and</nlm:aff></affiliation></author><author><name sortKey="Yoshimatsu, Yasuhiro" sort="Yoshimatsu, Yasuhiro" uniqKey="Yoshimatsu Y" first="Yasuhiro" last="Yoshimatsu">Yasuhiro Yoshimatsu</name><affiliation><nlm:aff id="aff1">Departments of *Molecular Pathology and</nlm:aff></affiliation></author><author><name sortKey="Imaizumi, Natsuko" sort="Imaizumi, Natsuko" uniqKey="Imaizumi N" first="Natsuko" last="Imaizumi">Natsuko Imaizumi</name><affiliation><nlm:aff id="aff1">Departments of *Molecular Pathology and</nlm:aff></affiliation></author><author><name sortKey="Masui, Shinji" sort="Masui, Shinji" uniqKey="Masui S" first="Shinji" last="Masui">Shinji Masui</name><affiliation wicri:level="1"><nlm:aff id="aff3">Laboratory for Pluripotent Cell Studies, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan;</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Laboratory for Pluripotent Cell Studies, RIKEN Center for Developmental Biology, Kobe 650-0047</wicri:regionArea><wicri:noRegion>Kobe 650-0047</wicri:noRegion></affiliation></author><author><name sortKey="Hirashima, Masanori" sort="Hirashima, Masanori" uniqKey="Hirashima M" first="Masanori" last="Hirashima">Masanori Hirashima</name><affiliation wicri:level="1"><nlm:aff id="aff4">Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Shinanomachi, Tokyo 160-8582, Japan;</nlm:aff><country 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Kantō</region></placeName></affiliation></author><author><name sortKey="Oike, Yuichi" sort="Oike, Yuichi" uniqKey="Oike Y" first="Yuichi" last="Oike">Yuichi Oike</name><affiliation wicri:level="1"><nlm:aff id="aff4">Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Shinanomachi, Tokyo 160-8582, Japan;</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Shinanomachi, Tokyo 160-8582</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Araie, Makoto" sort="Araie, Makoto" uniqKey="Araie M" first="Makoto" last="Araie">Makoto Araie</name><affiliation wicri:level="4"><nlm:aff id="aff2">Ophthalmology, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan;</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Ophthalmology, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region><settlement type="city">Tokyo</settlement></placeName><orgName type="university">Université de Tokyo</orgName></affiliation></author><author><name sortKey="Niwa, Hitoshi" sort="Niwa, Hitoshi" uniqKey="Niwa H" first="Hitoshi" last="Niwa">Hitoshi Niwa</name><affiliation wicri:level="1"><nlm:aff id="aff3">Laboratory for Pluripotent Cell Studies, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan;</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Laboratory for Pluripotent Cell Studies, RIKEN Center for Developmental Biology, Kobe 650-0047</wicri:regionArea><wicri:noRegion>Kobe 650-0047</wicri:noRegion></affiliation></author><author><name sortKey="Kubo, Hajime" sort="Kubo, Hajime" uniqKey="Kubo H" first="Hajime" last="Kubo">Hajime Kubo</name><affiliation wicri:level="4"><nlm:aff wicri:cut="; and" id="aff5">Molecular and Cancer Research Unit, Horizontal Medical Research Organization (HMRO), Graduate School of Medicine, Kawaramachi, Kyoto University, Kyoto 606-8501, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Molecular and Cancer Research Unit, Horizontal Medical Research Organization (HMRO), Graduate School of Medicine, Kawaramachi, Kyoto University, Kyoto 606-8501</wicri:regionArea><orgName type="university">Université de Kyoto</orgName><placeName><settlement type="city">Kyoto</settlement><region type="prefecture">Région du Kansai</region></placeName></affiliation></author><author><name sortKey="Suda, Toshio" sort="Suda, Toshio" uniqKey="Suda T" first="Toshio" last="Suda">Toshio Suda</name><affiliation wicri:level="1"><nlm:aff id="aff4">Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Shinanomachi, Tokyo 160-8582, Japan;</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Shinanomachi, Tokyo 160-8582</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Miyazono, Kohei" sort="Miyazono, Kohei" uniqKey="Miyazono K" first="Kohei" last="Miyazono">Kohei Miyazono</name><affiliation><nlm:aff id="aff1">Departments of *Molecular Pathology and</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="aff6">Department of Biochemistry, The Cancer Institute of the Japanese Foundation for Cancer Research, Ariake, Tokyo 135-8550, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Biochemistry, The Cancer Institute of the Japanese Foundation for Cancer Research, Ariake, Tokyo 135-8550</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">17287396</idno><idno type="pmc">1838981</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1838981</idno><idno type="RBID">PMC:1838981</idno><idno type="doi">10.1091/mbc.E06-09-0780</idno><date when="2007">2007</date><idno type="wicri:Area/Pmc/Corpus">003085</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">003085</idno><idno type="wicri:Area/Pmc/Curation">003084</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">003084</idno><idno type="wicri:Area/Pmc/Checkpoint">003A97</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">003A97</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Prox1 Induces Lymphatic Endothelial Differentiation via Integrin α9 and Other Signaling Cascades<xref ref-type="fn" rid="FN1"><sup><inline-graphic xlink:href="dbox.jpg" mimetype="image"></inline-graphic><inline-graphic xlink:href="vbox.jpg" mimetype="image"></inline-graphic></sup></xref></title><author><name sortKey="Mishima, Koichi" sort="Mishima, Koichi" uniqKey="Mishima K" first="Koichi" last="Mishima">Koichi Mishima</name><affiliation><nlm:aff id="aff1">Departments of *Molecular Pathology and</nlm:aff></affiliation><affiliation wicri:level="4"><nlm:aff id="aff2">Ophthalmology, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan;</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Ophthalmology, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region><settlement type="city">Tokyo</settlement></placeName><orgName type="university">Université de Tokyo</orgName></affiliation></author><author><name sortKey="Watabe, Tetsuro" sort="Watabe, Tetsuro" uniqKey="Watabe T" first="Tetsuro" last="Watabe">Tetsuro Watabe</name><affiliation><nlm:aff id="aff1">Departments of *Molecular Pathology and</nlm:aff></affiliation></author><author><name sortKey="Saito, Akira" sort="Saito, Akira" uniqKey="Saito A" first="Akira" last="Saito">Akira Saito</name><affiliation><nlm:aff id="aff1">Departments of *Molecular Pathology and</nlm:aff></affiliation></author><author><name sortKey="Yoshimatsu, Yasuhiro" sort="Yoshimatsu, Yasuhiro" uniqKey="Yoshimatsu Y" first="Yasuhiro" last="Yoshimatsu">Yasuhiro Yoshimatsu</name><affiliation><nlm:aff id="aff1">Departments of *Molecular Pathology and</nlm:aff></affiliation></author><author><name sortKey="Imaizumi, Natsuko" sort="Imaizumi, Natsuko" uniqKey="Imaizumi N" first="Natsuko" last="Imaizumi">Natsuko Imaizumi</name><affiliation><nlm:aff id="aff1">Departments of *Molecular Pathology and</nlm:aff></affiliation></author><author><name sortKey="Masui, Shinji" sort="Masui, Shinji" uniqKey="Masui S" first="Shinji" last="Masui">Shinji Masui</name><affiliation wicri:level="1"><nlm:aff id="aff3">Laboratory for Pluripotent Cell Studies, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan;</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Laboratory for Pluripotent Cell Studies, RIKEN Center for Developmental Biology, Kobe 650-0047</wicri:regionArea><wicri:noRegion>Kobe 650-0047</wicri:noRegion></affiliation></author><author><name sortKey="Hirashima, Masanori" sort="Hirashima, Masanori" uniqKey="Hirashima M" first="Masanori" last="Hirashima">Masanori Hirashima</name><affiliation wicri:level="1"><nlm:aff id="aff4">Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Shinanomachi, Tokyo 160-8582, Japan;</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Shinanomachi, Tokyo 160-8582</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Morisada, Tohru" sort="Morisada, Tohru" uniqKey="Morisada T" first="Tohru" last="Morisada">Tohru Morisada</name><affiliation wicri:level="1"><nlm:aff id="aff4">Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Shinanomachi, Tokyo 160-8582, Japan;</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Shinanomachi, Tokyo 160-8582</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Oike, Yuichi" sort="Oike, Yuichi" uniqKey="Oike Y" first="Yuichi" last="Oike">Yuichi Oike</name><affiliation wicri:level="1"><nlm:aff id="aff4">Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Shinanomachi, Tokyo 160-8582, Japan;</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Shinanomachi, Tokyo 160-8582</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Araie, Makoto" sort="Araie, Makoto" uniqKey="Araie M" first="Makoto" last="Araie">Makoto Araie</name><affiliation wicri:level="4"><nlm:aff id="aff2">Ophthalmology, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan;</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Ophthalmology, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region><settlement type="city">Tokyo</settlement></placeName><orgName type="university">Université de Tokyo</orgName></affiliation></author><author><name sortKey="Niwa, Hitoshi" sort="Niwa, Hitoshi" uniqKey="Niwa H" first="Hitoshi" last="Niwa">Hitoshi Niwa</name><affiliation wicri:level="1"><nlm:aff id="aff3">Laboratory for Pluripotent Cell Studies, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan;</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Laboratory for Pluripotent Cell Studies, RIKEN Center for Developmental Biology, Kobe 650-0047</wicri:regionArea><wicri:noRegion>Kobe 650-0047</wicri:noRegion></affiliation></author><author><name sortKey="Kubo, Hajime" sort="Kubo, Hajime" uniqKey="Kubo H" first="Hajime" last="Kubo">Hajime Kubo</name><affiliation wicri:level="4"><nlm:aff wicri:cut="; and" id="aff5">Molecular and Cancer Research Unit, Horizontal Medical Research Organization (HMRO), Graduate School of Medicine, Kawaramachi, Kyoto University, Kyoto 606-8501, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Molecular and Cancer Research Unit, Horizontal Medical Research Organization (HMRO), Graduate School of Medicine, Kawaramachi, Kyoto University, Kyoto 606-8501</wicri:regionArea><orgName type="university">Université de Kyoto</orgName><placeName><settlement type="city">Kyoto</settlement><region type="prefecture">Région du Kansai</region></placeName></affiliation></author><author><name sortKey="Suda, Toshio" sort="Suda, Toshio" uniqKey="Suda T" first="Toshio" last="Suda">Toshio Suda</name><affiliation wicri:level="1"><nlm:aff id="aff4">Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Shinanomachi, Tokyo 160-8582, Japan;</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Shinanomachi, Tokyo 160-8582</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Miyazono, Kohei" sort="Miyazono, Kohei" uniqKey="Miyazono K" first="Kohei" last="Miyazono">Kohei Miyazono</name><affiliation><nlm:aff id="aff1">Departments of *Molecular Pathology and</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="aff6">Department of Biochemistry, The Cancer Institute of the Japanese Foundation for Cancer Research, Ariake, Tokyo 135-8550, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Biochemistry, The Cancer Institute of the Japanese Foundation for Cancer Research, Ariake, Tokyo 135-8550</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author></analytic><series><title level="j">Molecular Biology of the Cell</title><idno type="ISSN">1059-1524</idno><imprint><date when="2007">2007</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>During embryonic lymphatic development, a homeobox transcription factor Prox1 plays important roles in sprouting and migration of a subpopulation of blood vessel endothelial cells (BECs) toward VEGF-C–expressing cells. However, effects of Prox1 on endothelial cellular behavior remain to be elucidated. Here, we show that Prox1, via induction of integrin α9 expression, inhibits sheet formation and stimulates motility of endothelial cells. Prox1-expressing BECs preferentially migrated toward VEGF-C via up-regulation of the expression of integrin α9 and VEGF receptor 3 (VEGFR3). In mouse embryos, expression of VEGFR3 and integrin α9 is increased in Prox1-expressing lymphatic endothelial cells (LECs) compared with BECs. Knockdown of Prox1 expression in human LECs led to decrease in the expression of integrin α9 and VEGFR3, resulting in the decreased chemotaxes toward VEGF-C. These findings suggest that Prox1 plays important roles in conferring and maintaining the characteristics of LECs by modulating multiple signaling cascades and that integrin α9 may function as a key regulator of lymphangiogenesis acting downstream of Prox1.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Mol Biol Cell</journal-id><journal-id journal-id-type="publisher-id">Mol. Bio. Cell</journal-id><journal-title>Molecular Biology of the Cell</journal-title><issn pub-type="ppub">1059-1524</issn><publisher><publisher-name>The American Society for Cell Biology</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">17287396</article-id><article-id pub-id-type="pmc">1838981</article-id><article-id pub-id-type="publisher-id">3196979</article-id><article-id pub-id-type="doi">10.1091/mbc.E06-09-0780</article-id><article-categories><subj-group subj-group-type="heading"><subject>Articles</subject></subj-group></article-categories><title-group><article-title>Prox1 Induces Lymphatic Endothelial Differentiation via Integrin α9 and Other Signaling Cascades<xref ref-type="fn" rid="FN1"><sup><inline-graphic xlink:href="dbox.jpg" mimetype="image"></inline-graphic><inline-graphic xlink:href="vbox.jpg" mimetype="image"></inline-graphic></sup></xref></article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Mishima</surname><given-names>Koichi</given-names></name><xref rid="aff1" ref-type="aff">*</xref><xref rid="aff2" ref-type="aff"><sup>†</sup></xref></contrib><contrib contrib-type="author"><name><surname>Watabe</surname><given-names>Tetsuro</given-names></name><xref rid="aff1" ref-type="aff">*</xref></contrib><contrib contrib-type="author"><name><surname>Saito</surname><given-names>Akira</given-names></name><xref rid="aff1" ref-type="aff">*</xref></contrib><contrib contrib-type="author"><name><surname>Yoshimatsu</surname><given-names>Yasuhiro</given-names></name><xref rid="aff1" ref-type="aff">*</xref></contrib><contrib contrib-type="author"><name><surname>Imaizumi</surname><given-names>Natsuko</given-names></name><xref rid="aff1" ref-type="aff">*</xref></contrib><contrib contrib-type="author"><name><surname>Masui</surname><given-names>Shinji</given-names></name><xref rid="aff3" ref-type="aff"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hirashima</surname><given-names>Masanori</given-names></name><xref rid="aff4" ref-type="aff"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Morisada</surname><given-names>Tohru</given-names></name><xref rid="aff4" ref-type="aff"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Oike</surname><given-names>Yuichi</given-names></name><xref rid="aff4" ref-type="aff"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Araie</surname><given-names>Makoto</given-names></name><xref rid="aff2" ref-type="aff"><sup>†</sup></xref></contrib><contrib contrib-type="author"><name><surname>Niwa</surname><given-names>Hitoshi</given-names></name><xref rid="aff3" ref-type="aff"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kubo</surname><given-names>Hajime</given-names></name><xref rid="aff5" ref-type="aff"><sup>‖</sup></xref></contrib><contrib contrib-type="author"><name><surname>Suda</surname><given-names>Toshio</given-names></name><xref rid="aff4" ref-type="aff"><sup>§</sup></xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Miyazono</surname><given-names>Kohei</given-names></name><xref rid="aff1" ref-type="aff">*</xref><xref rid="aff6" ref-type="aff"><sup>¶</sup></xref></contrib><aff id="aff1">Departments of *Molecular Pathology and</aff><aff id="aff2"><sup>†</sup>Ophthalmology, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan;</aff><aff id="aff3"><sup>‡</sup>Laboratory for Pluripotent Cell Studies, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan;</aff><aff id="aff4"><sup>§</sup>Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Shinanomachi, Tokyo 160-8582, Japan;</aff><aff id="aff5"><sup>‖</sup>Molecular and Cancer Research Unit, Horizontal Medical Research Organization (HMRO), Graduate School of Medicine, Kawaramachi, Kyoto University, Kyoto 606-8501, Japan; and</aff><aff id="aff6"><sup>¶</sup>Department of Biochemistry, The Cancer Institute of the Japanese Foundation for Cancer Research, Ariake, Tokyo 135-8550, Japan</aff></contrib-group><contrib-group><contrib contrib-type="editor"><name><surname>Margolis</surname><given-names>Ben</given-names></name><role>Monitoring Editor</role></contrib></contrib-group><author-notes><corresp>Address correspondence to: Kohei Miyazono (<email>miyazono-ind@umin.ac.jp</email>)</corresp></author-notes><pub-date pub-type="ppub"><month>4</month><year>2007</year></pub-date><volume>18</volume><issue>4</issue><fpage>1421</fpage><lpage>1429</lpage><history><date date-type="received"><day>5</day><month>9</month><year>2006</year></date><date date-type="rev-recd"><day>2</day><month>1</month><year>2007</year></date><date date-type="accepted"><day>31</day><month>1</month><year>2007</year></date></history><copyright-statement>© 2007 by The American Society for Cell Biology</copyright-statement><copyright-year>2007</copyright-year><self-uri xlink:title="pdf" xlink:href="zmk00407001421.pdf"></self-uri><abstract><p>During embryonic lymphatic development, a homeobox transcription factor Prox1 plays important roles in sprouting and migration of a subpopulation of blood vessel endothelial cells (BECs) toward VEGF-C–expressing cells. However, effects of Prox1 on endothelial cellular behavior remain to be elucidated. Here, we show that Prox1, via induction of integrin α9 expression, inhibits sheet formation and stimulates motility of endothelial cells. Prox1-expressing BECs preferentially migrated toward VEGF-C via up-regulation of the expression of integrin α9 and VEGF receptor 3 (VEGFR3). In mouse embryos, expression of VEGFR3 and integrin α9 is increased in Prox1-expressing lymphatic endothelial cells (LECs) compared with BECs. Knockdown of Prox1 expression in human LECs led to decrease in the expression of integrin α9 and VEGFR3, resulting in the decreased chemotaxes toward VEGF-C. These findings suggest that Prox1 plays important roles in conferring and maintaining the characteristics of LECs by modulating multiple signaling cascades and that integrin α9 may function as a key regulator of lymphangiogenesis acting downstream of Prox1.</p></abstract><custom-meta-wrap><custom-meta><meta-name>PDF</meta-name><meta-value><uri xlink:type="simple" xlink:href="zmk00407001421.pdf"></uri></meta-value></custom-meta></custom-meta-wrap></article-meta></front></pmc><affiliations><list><country><li>Japon</li></country><region><li>Région de Kantō</li><li>Région du Kansai</li></region><settlement><li>Kyoto</li><li>Tokyo</li></settlement><orgName><li>Université de Kyoto</li><li>Université de Tokyo</li></orgName></list><tree><noCountry><name sortKey="Imaizumi, Natsuko" sort="Imaizumi, Natsuko" uniqKey="Imaizumi N" first="Natsuko" last="Imaizumi">Natsuko Imaizumi</name><name sortKey="Saito, Akira" sort="Saito, Akira" uniqKey="Saito A" first="Akira" last="Saito">Akira Saito</name><name sortKey="Watabe, Tetsuro" sort="Watabe, Tetsuro" uniqKey="Watabe T" first="Tetsuro" last="Watabe">Tetsuro Watabe</name><name sortKey="Yoshimatsu, Yasuhiro" sort="Yoshimatsu, Yasuhiro" uniqKey="Yoshimatsu Y" first="Yasuhiro" last="Yoshimatsu">Yasuhiro Yoshimatsu</name></noCountry><country name="Japon"><region name="Région de Kantō"><name sortKey="Mishima, Koichi" sort="Mishima, Koichi" uniqKey="Mishima K" first="Koichi" last="Mishima">Koichi Mishima</name></region><name sortKey="Araie, Makoto" sort="Araie, Makoto" uniqKey="Araie M" first="Makoto" last="Araie">Makoto Araie</name><name sortKey="Hirashima, Masanori" sort="Hirashima, Masanori" uniqKey="Hirashima M" first="Masanori" last="Hirashima">Masanori Hirashima</name><name sortKey="Kubo, Hajime" sort="Kubo, Hajime" uniqKey="Kubo H" first="Hajime" last="Kubo">Hajime Kubo</name><name sortKey="Masui, Shinji" sort="Masui, Shinji" uniqKey="Masui S" first="Shinji" last="Masui">Shinji Masui</name><name sortKey="Miyazono, Kohei" sort="Miyazono, Kohei" uniqKey="Miyazono K" first="Kohei" last="Miyazono">Kohei Miyazono</name><name sortKey="Morisada, Tohru" sort="Morisada, Tohru" uniqKey="Morisada T" first="Tohru" last="Morisada">Tohru Morisada</name><name sortKey="Niwa, Hitoshi" sort="Niwa, Hitoshi" uniqKey="Niwa H" first="Hitoshi" last="Niwa">Hitoshi Niwa</name><name sortKey="Oike, Yuichi" sort="Oike, Yuichi" uniqKey="Oike Y" first="Yuichi" last="Oike">Yuichi Oike</name><name sortKey="Suda, Toshio" sort="Suda, Toshio" uniqKey="Suda T" first="Toshio" last="Suda">Toshio Suda</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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