Table 3 Lymphangiogenesis: genes involved in lymphatic vasculature formation
Gene | Function | Expression and function | Lymphatic phenotype |
|---|---|---|---|
Ang2 | Growth factor, ligand of Tie-2 | Lymphatics express Tie receptor family members. Smooth muscle cells of large vessels. The endothelium of smaller vessels at sites of vacular remodelling induces its expression. | Hypoplasia, chylous ascites |
D6 | β-chemokine receptor D6 | It may play a role in chemokine-driven leukocyte recycling through the lymphatics. | No available animal model |
FoxC2 | Forkhead/winged-helix transcription factor | Paraxial, presomitic mesodermic and developing somites. Later restricted to condensing mesenchyme of the vertebrae, head, limbs, and kidney. | Abnormal lymphatic pattern, absent valves, lymphatic vessel and lymph node hyperplasia. It is related to lymphedema-distichiasis |
Elk3 (Net) | Transcription factor | Expressed by the embryonic and adult vasculature: LECs and muscle layer in the thoracic duct, intestine and skin lymphatic vessels in mid-gestation. | Lymphangiectasis, chylothorax |
Lyve1 | Lymphatic vessel endothelial hyaluronan receptor-1 (CD44 homolog) | Embryonic and adult LECs. Hypothesized to function in the transport of hyaluronan. | Not available |
Nrp2 | Non-tyrosine kinase receptor for VEGF165, VEGF145, PIGF, VEGF-C and class 3 semaphorins | Embryonic and adult LECs. | Transient hypoplasia of lymphatic capillaries. |
Podoplanin | Membrane glycoprotein | Embryonic and adult LECs. | Lymphangiectasis, abnormal lymph transport, lymphedema. Respiratory failure due to abnormal lung development. |
Prox1 | Homeobox transcription factor | Embryonic and adult LECs. Required for further differentiation of lymphatic "biased" cells to the fully differentiated form | No lymphatic vessels, chylous ascites, adult onset obesity. |
SLC | ? | Embryonic and adult LECs | Not available |
Vegfr3 | Receptor tyrosine kinase that mediates VEGF-C/D | BECs and LECs early development, down-regulated by BECs, but remains high in LECs later during embryogenesis. | Hypoplasia, chylous ascites. It is related to Milroy disease |
VEGFC | Growth factor, ligand of VEGFR3 | Mesenchymal cells around embryonic veins, activated macrophages, skeletal muscle cells, and smooth muscle cells surrounding large arteries. | No lymphatic vessels, hypoplasia, chylous ascites |
Tie2 | Receptor for Ang1 and Ang2? | Embryonic and adult LECs? | Lymphatic defect |