P309	Forkhead transcription factor Foxc2, mutated in lymphedema distichiasis, controls maturation of lymphatic vessels.
1T.V.Petrova, 1C.Norrmen, 1T.Tammela, 1T.Karpanen, 2N.Miura, 3R.Mellor, 3P.Mortimer, 1K.Alitalo
1Molecular and Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Helsinki, FI; 2Department of Biochemistry, Hamamatsu University School of Medicine, Japan, Hamamatsu, JP; 3Dermatology Unit, St. Georges Hospital Medical School, London, GB.

Lymphatic vessels are essential in removing and transporting interstitial fluid back to the blood circulation, and abnormal function of these vessels leads to tissue edema. During development, primary lymphatic vascular plexus is remodeled to give rise to lymphatic capillaries which lack associated mural cells, and collecting lymphatic vessels, characterized by the presence of smooth muscle cells and valves, which prevent backflow of the lymph. In lymphedema-distichiasis (LD) lymphatic vessel function fails because of mutations in the gene encoding for forkhead transcription factor FOXC2. We have found that that both LD patients and mice lacking Foxc2 show abnormal vascular patterning, increased pericyte investment of lymphatic vessels, agenesis of valves and lymphatic dysfunction. These results show that Foxc2 is essential for the morphogenesis of lymphatic valves and the establishment of a pericyte-free lymphatic capillary. We have carried out now a detailed analysis of lymphatic vascular maturation and stabilization during embryonic and postnatal development, and show that Foxc2 acts as master control gene in this process.

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