Transcriptional regulation of endothelial cell-specific Tie1 and Vegfr3 genes

8 REVIEW OF THE LITERATURE 9 1 ENDOTHELIAL RECEPTOR TYROSINE KINASES AND VASCULAR DEVELOPMENT..... 9 1.1 MOLECULAR STRUCTURE OF ENDOTHELIAL RECEPTOR TYROSINE KINASES AND THEIR LIGANDS........ 9 1.2 CARDIOVASCULAR SYSTEM 11 1.2.1 Blood vascular system 13 Development of the blood vessels 13 Vasculogenesis 13 Angiogenesis 15 Vascular maturation 18 Heterogeneity of the vascular endothelium 19 Angiogenesis in the adult 20 1.2.2 The lymphatic system 22 Development of the lymphatic vessels 22 Lymphangiogenesis in the adult 25 2 REGULATION OF ENDOTHELIAL CELL-SPECIFIC EXPRESSION OF GENES 26 2.1 CHARACTERIZATION OF REGULATORY ELEMENTS OF ENDOTHELIAL SPECIFIC GENES 26 2.1.1 The Tie genes 26 2.1.2 The VEGFR1 and VEGFR2 genes 28 2.1.3 The VE-cadherin, PECAM-1 and VWF genes 31 2.1.4 Other genes predominantly expressed in endothelial cells 34 2.2 TRANSCRIPTION FACTORS REGULATING ENDOTHELIAL GENE EXPRESSION 36 2.2.1 Ets factors 36 2.2.2 GATA factors 38 3 USE OF ENDOTHELIAL TARGETING ELEMENTS IN FUTURE GENE THERAPY 40 AIMS OF THE PRESENT STUDY 42 MATERIALS AND METHODS 43 RESULTS AND DISCUSSION 46 1. DNA ELEMENTS NEEDED FOR THE TIE1 PROMOTER ACTIVITY AND CELL TYPE SPECIFICITY (I) ......... 46 2. GENERATION OF FLUORESCENT TIE1 REPORTER MICE TO ALLOW MONITORING OF VASCULAR DEVELOPMENT AND ENDOTHELIAL CELL ISOLATION (II) 48 3. THE GENOMIC STRUCTURE AND PROMOTER REGION OF VEGFR3 (III) 50 4. FUTURE PROSPECTS 52 CONCLUDING REMARKS 54 ACKNOWLEDGEMENTS 56 REFERENCES 57