Lymphangiogenesis is the process that leads to the formation of lymphatic vessels from pre-
existing vessels. Vascular endothelial growth factor C (VEGF-C), the major lymphangiogenic
growth factor, is produced as an inactive precursor and needs to be proteolytically
processed into a mature form in order to activate its receptors VEGFR-3 and VEGFR-2. A
deficiency of VEGF-C during embryonic lymphangiogenesis results in embryonic lethality
due to the lack of lymphatic vasculature. Hennekam lymphangiectasia-lymphedema …

Background. Hennekam lymphangiectasia–lymphedema syndrome (OMIM 235510) is a
rare autosomal recessive disease, which is associated with mutations in the collagen-and
calcium-binding EGF domains 1 (CCBE1) gene. Because of the striking phenotypic similarity
of embryos lacking either the Ccbe1 gene or the lymphangiogenic growth factor Vegfc gene,
we searched for CCBE1 interactions with the VEGF-C growth factor signaling pathway,
which is critical in embryonic and adult lymphangiogenesis. Methods and Results. By …