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Lymphangiogenesis: genes involved in lymphatic vasculature formation |
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| Gene |
Function |
Expression and function |
Lymphatic phenotype |
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| 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 |
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Ang1: angiopoietin. D6: β-chemokine receptor. ELK3: ETS-domain protein (SRF accessory protein 2). FOXC2: forkhead box C2. Lyve1: lymphatic vessel endothelial hyaluronan receptor 1. Nrp2: neuropilin 2. Prox1: prospero related homeobox 1. SLC: secondary lymphoid chemokine. Tie2: endothelial cell-specific receptor. Vegfr3: vascular endothelial growth-factor receptor 3. VegfrC: vascular endothelial growth-factor receptor C. LEC: lymphatic endothelial cell. BEC: blood endothelial cell. | |||
Bellini et al. Orphanet Journal of Rare Diseases 2006 1:43 doi:10.1186/1750-1172-1-43 |
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