| Contributors | p. xi |
| Preface | p. xv |
| Heart Development in Drosophila | p. 1 |
| Introduction | p. 2 |
| Morphology of the Drosophila Heart | p. 2 |
| Genetic Control of Cardiac Induction | p. 4 |
| Cardiac Cell Specification and Differentiation | p. 7 |
| Control of Cardiac Cell Polarity and Morphogenesis | p. 14 |
| Myocyte Reprogramming During Metamorphosis | p. 16 |
| Cardiac Function and Cardiac Aging | p. 19 |
| Drosophila Model for Human Cardiac Disease | p. 20 |
| Conclusions and Perspectives | p. 21 |
| Acknowledgments | p. 22 |
| References | p. 22 |
| Morphogenesis of the Vertebrate Heart | p. 31 |
| Introduction | p. 32 |
| Early Heart Development | p. 33 |
| Chamber Development | p. 38 |
| Development of the Arterial and Venous Poles of the Heart | p. 45 |
| Development of the Cardiac Conduction System | p. 47 |
| Conclusions and Future Directions | p. 58 |
| References | p. 59 |
| Heart Development and T-box Transcription Factors: Lessons from Avian Embryos | p. 69 |
| Introduction | p. 70 |
| T-box Regulatory Networks and Cardiac Cell Lineage Development | p. 72 |
| T-box Regulation of Cardiac Valvuloseptal and Conduction System Development | p. 75 |
| T-box Gene Regulation of Cells that Migrate into the Heart | p. 78 |
| T-box Cofactors and Target Genes in the Developing Heart | p. 80 |
| T-box Regulatory Networks and Development of Other Organ Systems | p. 82 |
| Conclusions and Perspectives | p. 84 |
| Acknowledgments | p. 85 |
| References | p. 85 |
| Transcriptional Control of Cardiac Boundary Formation | p. 93 |
| Introduction | p. 94 |
| AV Boundary | p. 97 |
| Left-Right Boundary (First-Second Heart Fields) | p. 101 |
| Primary Myocardium-Chamber (or Working) Myocardium Boundary | p. 105 |
| Compact-Trabecular Myocardium Boundary | p. 107 |
| Conclusions and Future Directions | p. 107 |
| Acknowledgments | p. 109 |
| References | p. 109 |
| Signaling Pathways in Embryonic Heart Induction | p. 117 |
| Introduction | p. 118 |
| Embryology of Heart Induction | p. 120 |
| Step 1: Establishing the Organizing Centers: Canonical Wnts | p. 124 |
| Step 2: Mesoderm Induction | p. 127 |
| Step 3: Establishing the Precardiac Mesoderm | p. 130 |
| Step 4: Differentiation of the Cardiac Lineage into Beating Cardiomyocytes | p. 135 |
| Conclusions and Future Directions | p. 139 |
| Acknowledgments | p. 140 |
| References | p. 141 |
| Islet1 Progenitors in Developing and Postnatal Heart | p. 153 |
| Introduction | p. 154 |
| The LIM-Homeodomain Transcription Factor Isl1 Marks Cardiac Progenitors and Is Required for Development of the Early Heart Tube | p. 155 |
| Isl1 and Transcriptional Networks Required for Heart Development | p. 157 |
| Isl1 Marks a Diversity of Cardiovascular Lineages | p. 159 |
| Isl1 Protein Persists in Outflow Tract and Nodal Conduction Tissue of the Mid-Gestation Heart | p. 161 |
| Isl1 as a Marker of a Pluripotent Cardiovascular Progenitor | p. 161 |
| Conclusions | p. 162 |
| Future Challenges | p. 162 |
| References | p. 163 |
| Role of microRNAs in Cardiovascular Biology | p. 167 |
| Introduction | p. 168 |
| miRNA Biogenesis and Repressions of Target mRNAs | p. 168 |
| Expression and Regulation of Muscle-Specific miRNAs | p. 171 |
| Muscle-Specific miRNAs as Developmental Regulators | p. 171 |
| Myogenic miRNAs as Cell Cycle Regulators | p. 174 |
| miRNAs in the Adult Heart | p. 175 |
| Future Directions | p. 175 |
| Acknowledgments | p. 177 |
| References | p. 177 |
| Divergent Roles of Hedgehog and Fibroblast Growth Factor Signaling in Left-Right Development | p. 179 |
| Introduction: Brief Historical Perspective on Left-Right Asymmetry | p. 180 |
| Are the Functions of Major Cell-Cell Signaling Pathways, Hedgehog and FGF, Conserved in LR Development? | p. 183 |
| Conclusions | p. 195 |
| References | p. 196 |
| Development of the Conduction System: Picking up the Pace | p. 203 |
| Introduction | p. 204 |
| Historical Background and Basic Electrophysiology Principles | p. 204 |
| Development of the CCS | p. 207 |
| Electrical Activation of the Developing Heart | p. 208 |
| Conclusions | p. 213 |
| Acknowledgments | p. 215 |
| References | p. 215 |
| Transcriptional Control of the Cardiac Conduction System | p. 219 |
| An Introduction to the Cardiac Conduction System | p. 220 |
| Developmental Origin and Induction of the Conduction System | p. 233 |
| Transcriptional Regulation of Conduction System Patterning and Function | p. 241 |
| Conclusions | p. 251 |
| Acknowledgments | p. 252 |
| References | p. 252 |
| Genetic Dissection of Hematopoiesis Using Drosophila as a Model System | p. 259 |
| Introduction | p. 260 |
| Drosophila Blood Cell Types | p. 264 |
| Blood Cell Origins in Drosophila | p. 266 |
| Embryonic Hematopoiesis | p. 267 |
| Larval Hematopoiesis | p. 273 |
| Modeling Hematopoietic Disease in Drosophila | p. 281 |
| Conclusions | p. 286 |
| Acknowledgments | p. 287 |
| References | p. 287 |
| Vascular Development in the Zebrafish | p. 301 |
| Introduction | p. 302 |
| Endothelial Fate Specification and Vasculogenesis | p. 304 |
| Arterial-Venous Specification | p. 308 |
| Lymphatic Development | p. 312 |
| Blood Vessel Lumen Formation | p. 316 |
| Patterning and Guidance | p. 318 |
| Blood Vessels and Organogenesis | p. 324 |
| Conclusions | p. 326 |
| Acknowledgments | p. 327 |
| References | p. 327 |
| Development and Function of the Epicardium | p. 333 |
| Introduction | p. 334 |
| Origin of the Epicardium | p. 335 |
| Contribution of the Epicardium to the Coronary Vasculature and Cardiac Growth | p. 342 |
| Genetics of Epicardial Development and Coronary Arteriogenesis | p. 349 |
| Conclusion | p. 352 |
| References | p. 352 |
| Genetics of Transcription Factor Mutations | p. 359 |
| Introduction | p. 360 |
| What is CHD? | p. 360 |
| Human Genetic Study Designs | p. 361 |
| Cardiac Transcription Factors Identified by Genetic Studies | p. 368 |
| Conclusions | p. 372 |
| Acknowledgments | p. 373 |
| References | p. 373 |
| Human Genetics of Congenital Heart Disease | p. 379 |
| Introduction | p. 380 |
| Heart Development | p. 381 |
| Natural History of Congenital Heart Disease | p. 382 |
| Valvar Abnormalities | p. 384 |
| Obstruction of the Great Vessels | p. 391 |
| Abnormal Communication Between Chambers or Great Arteries | p. 393 |
| Patent Ductus Arteriosus | p. 399 |
| Endocardial Cushion Defects | p. 401 |
| Complex CHD | p. 401 |
| Summary | p. 406 |
| References | p. 406 |
| Index | p. 419 |
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