Journal article
Ccbe1 regulates Vegfc-mediated induction of Vegfr3 signaling during embryonic lymphangiogenesis
L Le Guen, T Karpanen, D Schulte, NC Harris, K Koltowska, G Roukens, NI Bower, A van Impel, SA Stacker, MG Achen, S Schulte-Merker, BM Hogan
Development Cambridge | COMPANY BIOLOGISTS LTD | Published : 2014
DOI: 10.1242/dev.100495
Abstract
The VEGFC/VEGFR3 signaling pathway is essential for lymphangiogenesis (the formation of lymphatic vessels from preexisting vasculature) during embryonic development, tissue regeneration and tumor progression. The recently identified secreted protein CCBE1 is indispensible for lymphangiogenesis during development. The role of CCBE1 orthologs is highly conserved in zebrafish, mice and humans with mutations in CCBE1 causing generalized lymphatic dysplasia and lymphedema (Hennekam syndrome). To date, the mechanism by which CCBE1 acts remains unknown. Here, we find that ccbe1 genetically interacts with both vegfc and vegfr3 in zebrafish. In the embryo, phenotypes driven by increased Vegfc are sup..
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Funding Acknowledgements
This work was supported by an Australian Research Council Future Fellowship [FT100100165 to B.M.H.]; a European Molecular Biology Organization Long-Term Fellowship [LTRF 52-2007 to T.K.]; Veni grants from The Netherlands Organisation for Scientific Research (NWO) [916.10.132 to T.K.; 863.11.022 to G.R.]; Marie Curie Intra-European Fellowships (to D.S. and A.v.I.); National Health and Medical Research Council of Australia (NHMRC) project grants [631657 and APP1050138]; a Program Grant [487900 to M.G.A. and S.A.S.] and Research Fellowships (to M.G.A. and S.A.S.) from the National Health and Medical Research Council; and KNAW (S.S.-M.).