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Article: Sox18 induces development of the lymphatic vasculature in mice

TitleSox18 induces development of the lymphatic vasculature in mice
Authors
Issue Date2008
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/nature
Citation
Nature, 2008, v. 456 n. 7222, p. 643-647 How to Cite?
AbstractThe lymphatic system plays a key role in tissue fluid regulation and tumour metastasis, and lymphatic defects underlie many pathological states including lymphoedema, lymphangiectasia, lymphangioma and lymphatic dysplasia. However, the origins of the lymphatic system in the embryo, and the mechanisms that direct growth of the network of lymphatic vessels, remain unclear. Lymphatic vessels are thought to arise from endothelial precursor cells budding from the cardinal vein under the influence of the lymphatic hallmark gene Prox1 (prospero homeobox 1; ref. 4). Defects in the transcription factor gene SOX18 (SRY (sex determining region Y) box 18) cause lymphatic dysfunction in the human syndrome hypotrichosis-lymphoedema-telangiectasia, suggesting that Sox18 may also play a role in lymphatic development or function. Here we use molecular, cellular and genetic assays in mice to show that Sox18 acts as a molecular switch to induce differentiation of lymphatic endothelial cells. Sox18 is expressed in a subset of cardinal vein cells that later co-express Prox1 and migrate to form lymphatic vessels. Sox18 directly activates Prox1 transcription by binding to its proximal promoter. Overexpression of Sox18 in blood vascular endothelial cells induces them to express Prox1 and other lymphatic endothelial markers, while Sox18-null embryos show a complete blockade of lymphatic endothelial cell differentiation from the cardinal vein. Our findings demonstrate a critical role for Sox18 in developmental lymphangiogenesis, and suggest new avenues to investigate for therapeutic management of human lymphangiopathies. ©2008 Macmillan Publishers Limited. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/58263
ISSN
2015 Impact Factor: 38.138
2015 SCImago Journal Rankings: 21.936
ISI Accession Number ID
Funding AgencyGrant Number
National Health and Medical Research Council (Australia)
INSERM ( France)
Associazione Italiana per la Ricerca sul Cancro (Italy)
European CommunityLSHG-CT-2004-503573
Pfizer Foundation (Australia)
Australia), the Research Grants Council ( Hong Kong)
Research Grants Council (Hong Kong)
Raelene Boyle Sporting Chance Foundation (Australia)
Royal Australasian College of Surgeons
Heart Foundation of Australia
Australian Research Council
Funding Information:

We thank A. Nagy, W. Abramow-Newerly, L. Naldini, P. Berta, A. Yap and J. Gamble for gifts of reagents. We also thank L. Bernard, L. Tizzoni and V. Dall'Olio for quantitative real- time PCR analysis, M. Chan and A. Pelling for antibody characterization, and S. Pizzi for technical assistance. Confocal microscopy was performed at the Australian Cancer Research Foundation Dynamic Imaging Centre for Cancer Biology. This work was supported by the National Health and Medical Research Council ( Australia), INSERM ( France), the Associazione Italiana per la Ricerca sul Cancro ( Italy), the European Community (LSHG-CT-2004-503573, Eustroke and Optistem networks), the Pfizer Foundation (Australia), the Research Grants Council (Hong Kong), the Raelene Boyle Sporting Chance Foundation ( Australia), the Royal Australasian College of Surgeons, the Heart Foundation of Australia, and the Australian Research Council.

References

 

DC FieldValueLanguage
dc.contributor.authorFrançois, Men_HK
dc.contributor.authorCaprini, Aen_HK
dc.contributor.authorHosking, Ben_HK
dc.contributor.authorOrsenigo, Fen_HK
dc.contributor.authorWilhelm, Den_HK
dc.contributor.authorBrowne, Cen_HK
dc.contributor.authorPaavonen, Ken_HK
dc.contributor.authorKarnezis, Ten_HK
dc.contributor.authorShayan, Ren_HK
dc.contributor.authorDownes, Men_HK
dc.contributor.authorDavidson, Ten_HK
dc.contributor.authorTutt, Den_HK
dc.contributor.authorCheah, KSEen_HK
dc.contributor.authorStacker, SAen_HK
dc.contributor.authorMuscat, GEOen_HK
dc.contributor.authorAchen, MGen_HK
dc.contributor.authorDejana, Een_HK
dc.contributor.authorKoopman, Pen_HK
dc.date.accessioned2010-05-31T03:27:02Z-
dc.date.available2010-05-31T03:27:02Z-
dc.date.issued2008en_HK
dc.identifier.citationNature, 2008, v. 456 n. 7222, p. 643-647en_HK
dc.identifier.issn0028-0836en_HK
dc.identifier.urihttp://hdl.handle.net/10722/58263-
dc.description.abstractThe lymphatic system plays a key role in tissue fluid regulation and tumour metastasis, and lymphatic defects underlie many pathological states including lymphoedema, lymphangiectasia, lymphangioma and lymphatic dysplasia. However, the origins of the lymphatic system in the embryo, and the mechanisms that direct growth of the network of lymphatic vessels, remain unclear. Lymphatic vessels are thought to arise from endothelial precursor cells budding from the cardinal vein under the influence of the lymphatic hallmark gene Prox1 (prospero homeobox 1; ref. 4). Defects in the transcription factor gene SOX18 (SRY (sex determining region Y) box 18) cause lymphatic dysfunction in the human syndrome hypotrichosis-lymphoedema-telangiectasia, suggesting that Sox18 may also play a role in lymphatic development or function. Here we use molecular, cellular and genetic assays in mice to show that Sox18 acts as a molecular switch to induce differentiation of lymphatic endothelial cells. Sox18 is expressed in a subset of cardinal vein cells that later co-express Prox1 and migrate to form lymphatic vessels. Sox18 directly activates Prox1 transcription by binding to its proximal promoter. Overexpression of Sox18 in blood vascular endothelial cells induces them to express Prox1 and other lymphatic endothelial markers, while Sox18-null embryos show a complete blockade of lymphatic endothelial cell differentiation from the cardinal vein. Our findings demonstrate a critical role for Sox18 in developmental lymphangiogenesis, and suggest new avenues to investigate for therapeutic management of human lymphangiopathies. ©2008 Macmillan Publishers Limited. All rights reserved.en_HK
dc.languageengen_HK
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/natureen_HK
dc.relation.ispartofNatureen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshBiological Markers - analysisen_HK
dc.subject.meshCell Differentiationen_HK
dc.subject.meshCell Movementen_HK
dc.subject.meshCells, Cultureden_HK
dc.subject.meshEdema - geneticsen_HK
dc.subject.meshEndothelial Cells - cytology - metabolismen_HK
dc.subject.meshEphrin-B2 - geneticsen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshGene Expression Regulation, Developmentalen_HK
dc.subject.meshHomeodomain Proteins - geneticsen_HK
dc.subject.meshHypotrichosis - geneticsen_HK
dc.subject.meshLymphangiogenesisen_HK
dc.subject.meshLymphatic Vessels - cytology - embryology - metabolismen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMiceen_HK
dc.subject.meshMice, Inbred C57BLen_HK
dc.subject.meshMice, Inbred CBAen_HK
dc.subject.meshPromoter Regions, Genetic - geneticsen_HK
dc.subject.meshSOXF Transcription Factors - deficiency - genetics - metabolismen_HK
dc.subject.meshTelangiectasis - geneticsen_HK
dc.subject.meshTumor Suppressor Proteins - geneticsen_HK
dc.subject.meshVascular Endothelial Growth Factor Receptor-3 - geneticsen_HK
dc.subject.meshVeins - cytologyen_HK
dc.titleSox18 induces development of the lymphatic vasculature in miceen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0028-0836&volume=456&issue=7222&spage=643&epage=7&date=2008&atitle=Sox18+induces+development+of+the+lymphatic+vasculature+in+miceen_HK
dc.identifier.emailCheah, KSE:hrmbdkc@hku.hken_HK
dc.identifier.authorityCheah, KSE=rp00342en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/nature07391en_HK
dc.identifier.pmid18931657-
dc.identifier.scopuseid_2-s2.0-57349142376en_HK
dc.identifier.hkuros154374en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-57349142376&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume456en_HK
dc.identifier.issue7222en_HK
dc.identifier.spage643en_HK
dc.identifier.epage647en_HK
dc.identifier.isiWOS:000261340000042-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.f10001124555-
dc.identifier.scopusauthoridFrançois, M=25228585700en_HK
dc.identifier.scopusauthoridCaprini, A=16551678500en_HK
dc.identifier.scopusauthoridHosking, B=6603918843en_HK
dc.identifier.scopusauthoridOrsenigo, F=6507692237en_HK
dc.identifier.scopusauthoridWilhelm, D=7006636008en_HK
dc.identifier.scopusauthoridBrowne, C=36926542200en_HK
dc.identifier.scopusauthoridPaavonen, K=6602911889en_HK
dc.identifier.scopusauthoridKarnezis, T=16068623000en_HK
dc.identifier.scopusauthoridShayan, R=14020600300en_HK
dc.identifier.scopusauthoridDownes, M=7005653144en_HK
dc.identifier.scopusauthoridDavidson, T=8245228100en_HK
dc.identifier.scopusauthoridTutt, D=25229444400en_HK
dc.identifier.scopusauthoridCheah, KSE=35387746200en_HK
dc.identifier.scopusauthoridStacker, SA=35444491800en_HK
dc.identifier.scopusauthoridMuscat, GEO=7006205187en_HK
dc.identifier.scopusauthoridAchen, MG=7004858757en_HK
dc.identifier.scopusauthoridDejana, E=7102657331en_HK
dc.identifier.scopusauthoridKoopman, P=7102712085en_HK
dc.identifier.citeulike3472366-

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