期刊
DEVELOPMENT
卷 141, 期 6, 页码 1239-U123出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.100495
关键词
Angiogenesis; Lymphangiogenesis; Lymphedema; Vasculature; Zebrafish
资金
- Australian Research Council Future Fellowship [FT100100165]
- European Molecular Biology Organization Long-Term Fellowship [LTRF 52-2007]
- Netherlands Organisation for Scientific Research (NWO) [916.10.132, 863.11.022]
- Marie Curie Intra-European Fellowships
- National Health and Medical Research Council of Australia (NHMRC) [631657, APP1050138]
- Research Fellowships from the National Health and Medical Research Council
- KNAW
- [487900]
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 suppressed in the absence of Ccbe1, and Vegfc-driven sprouting is enhanced by local Ccbe1 overexpression. Moreover, Vegfc- and Vegfr3-dependent Erk signaling is impaired in the absence of Ccbe1. Finally, CCBE1 is capable of upregulating the levels of fully processed, mature VEGFC in vitro and the overexpression of mature VEGFC rescues ccbe1 loss-of-function phenotypes in zebrafish. Taken together, these data identify Ccbe1 as a crucial component of the Vegfc/Vegfr3 pathway in the embryo.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据