Ccbe1

The lymphatic system comprises a vascular system separate from the cardiovascular system, essential for immune responses, fluid homeostasis and fat absorption. Lymphatic vessels develop in a complex process termed lymphangiogenesis that involves budding, migration and proliferation of lymphatic endothelial progenitor cells. A few genes, such as FLT4, FOXC2 and SOX18, are known to be critically involved in lymph vessel formation in humans. Lymphedema, lymphangiectasias, mental retardation and unusual facial characteristics define the autosomal recessive Hennekam syndrome. Homozygosity mapping identified a critical chromosomal region containing ccbe1, encoding Collagen and Calcium-Binding EGF-domain-1, a secreted protein which is required for embryonic lymphangiogenesis in zebrafish. ccbe1 is not expressed in endothelial cells of lymph vessels, and it may be a component of the extracellular matrix. In zebrafish, ccbe1 expression was observed along the earliest migration routes of endothelial cells that sprout from the posterior cardinal vein and migrate circuitously before developing into lymphatic vessels. ccbe1 might therefore be involved in guidance of these migrating cells.