INTRODUCING ZEBRAFISH AS A MODEL SYSTEM FOR STUDYING SOX18, A TRANSCRIPTION FACTOR LINKED TO HUMAN HYPOTRICHOSIS-LYMPHEDEMA-TELANGIECTASIA

HLT is a human genetic disease associated with mutations in the gene for SOX18, a protein that binds to DNA and controls the expression of other yet unidentified genes. SOX18 appears to regulate the development of hair, blood vessels and lymphatic vessels: these are altered in patients affected by HLT. Zebrafish, a small tropical fish kept in many aquaria, is being considered since a few years as a useful model system for studying vertebrate development and is now being used for unraveling the evolutionarily conserved mechanisms underlying many human diseases. Zebrafish is particularly suitable for studying normal blood-vessel development and defects in the circulatory system. It has been proposed that SOX18 is required for the development of the cells which form the internal wall of all vessels, the so-called endothelial cells. We plan to induce alterations in this protein , similar to those caused by mutations in patients affected by HLT, to study their effect on the development of endothelial cells in zebrafish embryos. At the same time, we will study how a mutated SOX18 changes the whole set of genes expressed by cells “induced”to become endothelial cells in a “test tube”, trying to identify the controlled genes. We expect that the data gathered in our study will prove useful for understanding some of the molecular defects underlying this human disease.