Heart development and regeneration

Heart development and regeneration 2

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adam_text Contents XVII Volume II List of Contributors Foreword Preface xxv xxix xxxi Part 9 Transcriptional Circuits in Cardiac Development and Disease 9.1. NK-2 Class Homeodomain Proteins: Conserved Regulators of Cardiogenesis David A. Elliott, Edwin P. Kirk, Daniel Schaft and Richard P. Harvey I. Introduction 569 II. Molecular Nature of Nkx2-5 571 H.A. Conserved Domains within NK-2 Genes 573 N.B. TheTN-Domain 573 U.C. NK-2 Specific Domain (NK2-SD) 573 11.D. Post-translational Modifications of Nkx2-5 574 III. Biochemical Interactions Between Nkx2-5 and Other Members of the Cardiac Gene Regulatory Network 575 III.A. GATA Factors 575 III.B. FoxM 575 lll.C. Т -box Proteins 576 III.D. Serum Response Factor 576 III.E. Nkx2-5 and Chromatin Remodeling Factors 576 IV. Nkx2-5 and Heart Disease 577 V. Phenotypes of Nkx2-5 Mutants in Mice 582 V.A. Nkx2-5 and the Patterning of the Vertebrate Heart 583 V.B. Nkx2-5 in the Establishment and Maintenance of Boundaries 585 V.C. Nkx2-5 and the Developing Ventricular Conduction System 586 V.D. Nkx2-5 Regulates Formation of the Endocardium 587 VI. Studies of Nkx2-5 in Other Vertebrate Model Systems 587 VII. Tinman and the Drosophila Dorsal Vessel 588 VIII. Regulatory Components of the Nkx2-5 Locus 589 IX. Conclusions 591 References 591 9.2. GATA4 in Heart Development and Disease Georges Nemer and Mona Nemer I. The GATA Family of Zinc-Finger Transcription Factors 599 I.A. Overview 599 I.B. General Properties 599 II. Expression of GATA Proteins in Cardiovascular Cells 600 H.A. The Two Subfamilies of Vertebrate GATA Proteins 600 II.B. GATA Proteins in the Myocardium 601 U.C. GATA Proteins in the Endocardium 602 II.D. GATA Proteins in the Outflow Tract 602 U.E. GATA Proteins in Other Cardiovascular Cells 603 III. Regulation of Cardiac GATA Factors 603 III.A. Regulation of Gene Expression 603 III.B. Regulation of Protein Activity 604 IV. Role of GATA Factors in Embryonic Heart Development 605 IVA. GATA4 605 IV.B. GATA5 606 IV.C. GATA6 606 V. Role of GATA Factors in Postnatal Heart Development 607 V.A. GATA4 and Cardiomyocyte Hypertrophy 607 V.B. GATA6 and Vascular Remodeling 608 VI. Role of GATA4 in Cardiomyocyte Survival 609 VII. Combinatorial Interactions of GATA Factors with Other Transcriptional Regulators 609 VILA. Cell-Specific GATA Collaborators 609 VII.B. Inducible GATA Co-Factors 611 VIII. GATA Factors as Integrators and Regulators of Cell Signaling in the Heart 611 IX. GATA4 and Congenital Heart Disease 612 X. Conclusion and Perspectives 612 References 613 9.3. Serum Response Factor and Co-Factors, Roles in Cardiac Development Robert J. Schwartz I. Introduction II. Serum Response Factor 617 617 XVIII Contents III. Embryonic Serum Response Factor Expression is Largely Restricted to Cardiac and Skeletal Muscle Tissues 619 IV. Serum Response Factor Orchestrates Cardiac Myogenesis 620 IV.A. Myogenic Contractile Proteins are Downregulated in Serum Response Factor-Null Embryonic Stem Cells 620 IV.B. Serum Response Factor Directs the Expression of Many MicroRNAs 622 V. Serum Response Factor in Human Heart Disease 623 V.A. Inhibitory Serum Response Factor is Generated by Caspase 3 Cleavage in Human Heart Failure 623 VI. Serum Response Factor Gene Autoregulation 624 VI.A. Tbx Factors Regulate Serum Response Factor Gene Activity through its 3 UTR Gene Enhancer 625 VII. Identification of Serum Response Factor Gene Targets 628 VILA. Serum Response Factor-Dependent Transactivation of DNA Targets Correlates Well With the Quality and Quantity of Serum Response Factor-Binding Sites 628 VII.B. Serum Response Factor Target Genes Raf1 , Map4k4 and Bicci Play Roles in Mesoderm Formation 629 VII.C Serum Response Factor Target Genes Play an Inductive Role in Cardiovascular Development 630 VIII. Combinatorial Interactions of Serum Response Factor-Accessory Proteins 630 VIII.A. Recruitment of the Tinman Homolog Nkx2-5 by Serum Response Factor-Activated Cardiac a-Actin Gene Transcription 633 VIII.B. GATA4 and Nkx2-5 Co-activate Nkx2-5 DNA-BindingTargets 634 VIII.C. Serum Response Factor and GATA4 are Mutual Co-Regulators 634 VIII.D. Competition between Negatively Acting YY1 versus Positively Acting Serum Response Factor Regulates a-Acti η Promoter Activity 635 IX. Hop, а Homeobox Protein Enriched in the Heart, Inhibits Serum Response Factor Myogenic Activity 63 7 X. Cysteine-Rich Protein LIM Factors Bridge Serum Response Factor with GATA6 and Activate Smooth Muscle Genes 637 XI. Serum Response Factor Co-activator Myocardin is Required for Vascular Smooth Muscle Development 639 XII. Serum Response Factor Mutants Block Sarcomerogenesis in Serum Response Factor-Null Embryonic Stem Cells 640 XIII. Post-Translational Modification of Serum Response Factor and Co-Factors are Important Regulatory Switches 640 XIII.A. Myocardin Sumoylation Transactivates Cardiogenic Genes 640 XIII.B. Role of Histone Deacetylases (HDACs) and Histone Acetyl- transferases (HATs) in Serum Response Factor-Dependent Muscle Gene Activity 642 XIII.C. Serum Response Factor MADS Box Serine-162 Phosphorylation Switches Proliferation and Myogenic Gene Programs 643 Xlll.D. Mimicking Phosphorylation of S1 62 in the MADS-box Permits с -fos Promoter Activity 643 References 645 9.4. Т -Box Factors Frank L Conlon and Katherine E. Yutzey 1. Introduction 651 II. Brachyury and the Т -Box Family of Proteins 651 H.A. 76x7 652 II.B. Tbx2 654 U.C. ТЬхЗ 654 II. D. Tbx5 655 U.E. Tbx18 656 II. F. Tbx20 657 III. Т -Box Genes and the Cardiac Cell-Cycle 658 IV. Т-Вох Regulation of Cardiac Gene Expression 660 IV.A. Т -Box Proteins Act as Repressors and Activators 660 IV.B. Т -Box Protein Transcriptional Partners 661 IV.C. Т -Box Protein Downstream Target Genes 662 V. Т -Box Regulatory Networks 662 V.A. Upstream Regulatory Pathways That Control Т -Box Gene Expression 662 V.B. Cross-Talk Among Т -Box Gene Family Members 663 VI. Т -Box Factors and Congenital Heart Malformations 663 VI.A. Holt-Oram Syndrome 663 VLB. DiGeorge Syndrome 664 VII. Summary and Future Directions 665 References 665 Contents XIX 9.5. Myocyte Enhancer Factor 2 Transcription Factors in Heart Development and Disease Brian L Black and Richard M. Cripps I. Introduction 673 II. The MEF2 Family of Transcription Factors 674 II.A. Discovery of MEF2 Transcription Factors 674 II.B. The MEF2 Family in the Context of the MADS Domain Superfamily 674 U.C. Structure of MEF2 Proteins 675 III. Regulation of MEF2 Activity by Post-Translational Modification 677 III.A. MEF2 Functions as a Transcriptional Co-Factor 677 III.B. Chromatin Remodeling by MEF2 through Interaction with Histone Deacetylases 678 III. C. MEF2 Functions as a Signal- Dependent Transcriptional Switch 680 IV. MEF2 Gene Function in the Heart and Other Tissues 682 IV.A. MEF2 Proteins are Expressed in Multiple Lineages During Development and in Adulthood 682 1V.B. Genetic Analyses of Mef2 Gene Function 683 IV.C. Direct Transcriptional Targets of MEF2 in the Heart 685 V. Regulation of MEF2 Gene Transcription 687 V.A. Mef2 Gene Regulation as a Paradigm for Modular Transcriptional Control 687 V.B. Regulation of Mef2 Transcription in the Drosophila Heart 688 V.C. Regulation of Mef2c Transcription in the Mammalian Heart 689 VI. Future Directions 691 References 692 PartiO Epigenetic Modifiers of Cardiac Development 10.1. Chromatin Modification and Remodeling in Heart Development H.A. Histone-Modifying Proteins 703 II.B. Chromatm-Remodeling Complexes 706 111. Histone-Modifying Enzymes in Heart Development 706 III.A. Histone Acetyl Transferases 706 III.B. Histone Deacetylases 707 III.C Histone Methylation/ Demethylation 707 III.D. Smydi: A Versatile Histone- Modifying Protein 708 III.E. Jumonji: A Cardiac Histone Demethylase? 708 IV. Pc Complexes and the Establishment of Cardiac Identity 708 IV.A. Pc Complexes in Stem Cells: Poising Genes for Lineage Activation? 708 lV.B. A Role for Pc Complexes in Heart Development? 709 V. Chromatin-Remodeling Complexes in Heart Development 709 V.A. Swi/Snf (BAF) Complexes: Baf60c and Heart Development 709 V.B. Swi/Snf (BAF) Complexes: Brgi and Heart Development 710 V.C. BAF Complexes: Baf250a and Heart Development 710 V.D. PBAF Complexes: Bafl 80 and Heart Development 711 V.E. Baf45c/DPF3 and Recognition of Histone Modifications 711 VI. Conclusions 711 References 711 Benoit G. Bruneau I. Introduction II. Chromatin Modification and Remodeling: General Concepts and Key Players 703 703 10.2. Histone Deacetylases in Cardiovascular Development and Disease Bryan D. Young and Eric N. Olson I. Histone Acetyl Transferases and Histone Deacetylases 715 II. Histone ОеасеЇуІаве-МЕРг Interaction 716 H.A. Histone Deacetylases as Repressors of MEF2-Mediated Transcription 716 N.B. MEF2-lndependent Functions for Class II Histone Deacetylases 717 III. Class II Histone Deacetylases as Regulators of Cardiac Remodeling 717 III.A. The Development-Hypertrophy Connection 717 IV. Signal-Dependent Regulation of Class II Histone Deacetylases 718 XX Contents V. Historie Deacetylase Kinases 718 V.A. Protein Kinase D 718 V.B. CaMKII 719 V.C. MARK Kinases 719 VI. Histone Deacetylase Knockout Mice 720 VIA HDAC9 and HDAC5 Knockout Mice 720 VLB. HDAC7 Knockout Mouse 721 VI.C. HDAC4 Knockout Mouse 722 VI. D. HDAC1 Knockout Phenotype 723 VII. Histone Deacetylase Inhibitors and Therapeutics 723 VILA. Histone Deacetylase Inhibitors 723 VII.B. Perspectives on Therapeutics 723 References 724 10.3. MicroRNA Regulation of Cardiac Development and Disease Kimberly R. Cordes and Deepak Srivastava I. Introduction 729 II. Biogenesis, Organization and Target Recognition of miRNA 730 III. The Function of miRNAs During Cardiogenesis 731 IV. Cardiac-and Muscle-Specific miRNAs 731 IVA. Organization and Regulation of miR-1 and miR-1 33 732 IV.B. Function oí miR-1 during Cardiogenesis 732 IV.C. Targeted Deletion of Mouse miR-1 -2 734 IV.D. miR-1 38 Regulation of Cardiac Patterning 736 IV.E. Targeted Deletion of miR-208 736 IV.F. Function of miR-206 and miR-1 81 736 V. Cardiac Stress-Responsive miRNAs 737 VI. miRNA Function During Angiogenesis 738 VII. Summary 738 References 738 Partii Cardiomìcs 11.1. Genomic Analyses in the Developing and Diseased Heart Shuaib Latif and Daniel J. Carry I. Introduction 743 II. Genomic Profiling Strategies 743 H.A. Conventional Methods for Cardiovascular Gene Discovery 743 III. Microarray Technologies 744 III.A. Complementary DNA (cDNA) Microarrays 744 111-B. Oligonucleotide Arrays 745 III.C. RNA Amplification 745 IV. Data Analysis and Bioinformatics 746 IV.A. Applications Utilizing Transcriptome Analysis 747 IV.B. Global Gene Expression in the Post-Injured Heart 748 IV.C. Global Gene Expression in the Hypertrophie and Failing Heart 750 References 750 11.2. Exploring the Genetic Basis for Congenital Heart Disease with Mouse ENU Mutagenesis Cecilia W. Lo, Qing Yu, Yuan Shen, Linda Leatherbury, Richard Francis, Xiao-Qing Zhao, Zhen Zhang, Andy Wessels, Guo-Ying Huang and Bishwanath Chatterjee I. Congenital Heart Disease 753 II. Modeling Congenital Heart Disease in Mice 754 III. Forward Genetic Screens 758 IV. Mouse Fetal Echocardiography Screening 759 IVA. Sagittal Views 759 IV.B. Frontal Views 759 IV.C. Transverse Views 761 V. Ultrasound Detection of Cardiovascular Defects 762 VI. Diagnosis of Structural Heart Defects 764 VII. Noncardiac Defects 765 VIII. Mapping Mutations and Strain Modifier Effects 766 IX. Mutation Identification 770 X. Mutation in Megf8 Causes Single Ventricle Spectrum of Complex Congenital Heart Disease 771 XI. DNAH5 Mutation, Heterotaxy and Primary Ciliary Dyskmesia 775 XII. Future Prospects for Saturation Mutagenesis Screens 776 References 776 11.3. Imaging Cardiac Developmental Malformations in the Mouse Embryo Timothy Mohun, Wolfgang Weninger and Shoumo Bhattacharya I. Introduction II. The Limits of Histology 779 779 Contents XXI III. The Promise of Optical Projection Tomography IV. Episcopie Imaging V. High Resolution Episcopie Microsocopy VI. High-Throughput Phenotyping VII. Magnetic Resonance Imaging VIII. Conclusions: A Phenotyping Pipeline References 11.4. Proteomic Strategies for Understanding Cardiac Function, Development, and Disease Charts Himeda and Steve Hauschka I. Introduction: The Need for Proteomics in Cardiac Analysis 793 II. Proteomics and Cardiac Disease 793 III. Proteomic Identification of Cardiac Transcription Factors 794 III.A. Source Material 795 III.B. Transcription Factor Enrichment 796 III.C. Transcription Factor Identification by Quantitative Proteomics 797 III.D. Confirmation of Candidates 800 IV. Future Prospects 800 References 801 11.5. Proteomic Analysis of MEF2 Post-Translational Regulation in the Heart David M. Cox, Min Du and John С McDermott I. Introduction 805 II. The Central Role of Mass Spectrometric Analysis in Proteomic Analysis of Protein-Protein Interactions 807 H.A. Purification of Multiprotein Complexes 807 III. Identification of Protein Complex Components by Mass Spectrometry 810 IV. Mass Spectrometry Instrumentation 812 IV.A. Operational Peptide Detection Modes 813 V. Identification of a MEF2A Interacting Protein 814 VI. Proteomic Analysis of Reversible Phosphorylation: A Rheostatic Control Mechanism for Transcription Factor Activity 815 VI.A. Precursor Ion and Neutral Loss Scanning 816 VLB. Multiple Reaction Monitoring 816 Vl.C. New Vistas: Quantitative 780 Analysis of Peptides 818 781 VLD. Phosphopeptide Analysis of MEF2A 818 782 VII. A Transition-State Model of MEF2 784 Regulation 819 786 References 820 788 789 Part 12 The Regenerative Heart 12.1. Evolution of Regeneration Jonathan M.W. Slack I. Introduction 827 II. Phylogeny of Animals 827 H.A. Distribution of Regenerative Ability 829 N.B. Technical Issues 831 U.C. Annelid Regeneration 831 II.D. Urodele Limb Regeneration 832 U.E. Mammalian Hyperplastic Regeneration 833 11.F. Cardiac Regeneration in Vertebrates 835 III. Conclusions 835 References 836 12.2. Cardiac Regeneration in the Zebrafish Model System Kenneth Poss I. Introduction 839 II. Regeneration 839 III. Capacity for Heart Regeneration 840 III.A. The Mammalian Heart 840 III.B. The Amphibian Heart 841 III.C. The Zebrafish Heart 841 IV. Myocardial Progenitor Cells and Zebrafish Heart Regeneration 842 IV.A. New Cardiomyocytes are Born during Heart Regeneration 842 IV.B. Participation of Progenitor Cells 843 IV.C. Possible Origins of Progenitor Cells 845 V. Nonmyocardial Cells and Heart Regeneration 845 VI. Molecular Genetic Approaches to Zebrafish Heart Regeneration 847 VII. Why does the Zebrafish Heart Regenerate? 849 VIII. Summary and Future Directions 851 References 851 XXII Contents Part 13 Properties of Cardiac Progenitor Cells 13.1. Detection and Identification of Tissue Stem Cells: Tracking an Elusive Prey Daniel C. Blackmore and Rodney L Rietze I. Introduction 857 II. What is a Stem Cell? 857 H.A. Associated Definitions and Concepts 858 II.B. Spiral Model of Stem Cell Differentiation 861 U.C. Are Ependymal Cells Stem Cells? 863 I I.D. Are Stem Cells a Subtype of Astrocytes? 867 III. Summary and Conclusions 870 References 870 13.2. Human Cardiomyocytes from Embryonic Stem Cells: Windows to Human Biology and Elements for Regeneration Charles E. Murry, Joseph Cold, Lil Pabon and Lior Gepstein I. Introduction 877 II. A Brief Overview of Human Embryonic Stem Cells 877 III. Embryoid Bodies and the Generation of Cardiomyocytes from Embryonic Stem Cells 879 III.A. Directed Differentiation of Cardiomyocytes 880 III.B. Ultrastructural and Electrophysiological Properties 882 111.C. Purification of Cardiomyocytes from Human Embryonic Stem Cell Cultures IV. Proliferation in Human Embryonic Stem y Cell-Derived Cardiomyocytes V. Transplantation Studies V.A. Transplantation into the Uninjured Heart V.B. Transplantation for Electrophysiological Repair V.C. Future Directions and a Road Map for Clinical Applications VI. Concluding Remarks References 884 886 887 887 888 890 892 892 Part 14 Driving Cardiac Regeneration 14.1. Adult Stem Cell-Based Therapy for the Heart Massimiliano Cnecchi and Victor) Dzau I. Introduction 899 II. Background 899 H.A. Pathology of Acute Myocardial Infarct: The Traditional View 900 N.B. New Concepts of Cardiac Homeostasis and Repair 900 III. Embryonic Versus Adult Stem Cells: Which Way to Go? 901 IV. Adult Stem Cells for Cardiac Repair 902 IV.A. Hematopoietic Stem Cells 902 IV.B. Endothelial Progenitor Cells 903 IV.C. Mesenchymal Stem Cells 905 V. Structural and Functional Effects of Bone Marrow-Derived Stem Cells on Animal Infarcted Hearts 907 VI. Mechanisms of Action of Bone Marrow-Derived Stem Cells in Cardiac Repair 907 VI.A. Cardiomyocyte Regeneration 912 VLB. Vasculogenesis 916 VI.C. Paracrine Effects 917 VII. Clinical Studies Testing Bone Marrow- Derived Cells for Ischemie Heart Disease 921 VIH. Outstanding Issues 928 References 929 14.2. Cell Therapy for Recapitulation of Vascular Network Formation and Functional Heart Muscle Recovery after Myocardial Ischemia Silviu Itescu and Stefanie Dimmeier I. Introduction 937 II. Strategies for the Use of Cellular Therapy to Improve Myocardial Function 938 III. Concomitant Induction of Vascular Structures Augments Survival and Function of Cardiomyocyte Precursors 938 IV. Formation of Vascular Structures During Embryogenesis: Interrelationship Between Endothelial Precursors and Pericytes 939 Contents XXIII V. Characterization of Endothelial Progenitor Cells (EPC) in Human Adult Bone Marrow and Their Use in Cardiac Ischemia 939 VI. Homing of Endothelial Precursor Cells to Ischemie Heart Tissue in Experimental and Clinical Studies 940 VII. Role of Chemokines in Endothelial Precursor Cell-Homing to Ischemie Myocardium 940 VIII. Role of Integrins in Adhesion and Transendothelial Migration of Endothelial Precursor Cells 941 IX. Role of Proteases in Endothelial Precursor Cell Mobilization and Homing 941 X. Strategies to Augment Endothelial Precursor Cell Homing and Engraftment 942 XI. Adult Bone Marrow Contains a Population of Multipotenţ Highly Proliferative and Clonogenic Mesenchymal Lineage Progenitors with Pericyte-Like Properties 942 XII. Distinctive Anatomical Location of STRO-I01^111 Mesenchymal Lineage Precursor Cells Suggests a Shared Identity with Vascular Pericytes 943 XIII. Human Mesenchymal Precursor Cells as Progenitors of the Vascular Network 943 XIV. STRO-1bH8ht Pericyte-Like Cells for Induction of Neovascularization and Treatment of Ischemie Heart Disease 944 XV. Potential for Allogeneic Use of Mesenchymal Lineage Precursor Cells 946 XVI. Conclusions 946 References 947 14.3. Cardiac Regeneration and Aging Annarosa Ieri, Jan Kajstura and Piero Anversa I. Introduction 11. Organ Homeostasis, Aging and Regeneration H.A. Stem Cell-Regulated Organs II.B. Stem Cell Aging 951 951 951 952 U.C. Regenerative Capacity of Adult Organs 954 III. Cellular, Organ and Organism Aging 956 III.A. Replicative Senescence 956 III.B. Replicative Senescence and the Myocardium 957 IV. Aging of the Heart 960 IV.A. The Aging Myocardium 960 IV.B. The Aging Myocardium and the Telomerase-Telomere System 962 IV.C. The Aging Myocardium and Cardiac Stem Cells 964 V. Cardiac Niches, Cardiac Stem/Progenitor Cell Ablation and Repopulation 967 V.A. Myocardial Aging and Cardiac Stem/Progenitor Cell Niches 967 V.B. Myocardial Aging, Cardiac Stem/ Progenitor Cell Niche Homeostasis and Cardiomyogenesis 970 V.C. Myocardial Aging and Cardiac Stem/Progenitor Cell Ablation and Repopulation 973 VI. Concluding Remarks 974 References 975 14.4. Genetic Enhancement of Cardiac Regeneration Enrique Lara-Pezzi and Nadia Rosenthal I. Introduction 981 II. Enhancing Cardiac Regeneration 982 H.A. Manipulation of the Cell-Cycle 982 II.B. Growth Factors 983 U.C. Extracellular Matrix Components and Other Secreted Proteins 986 III. Clinical Application of Regenerative Strategies 989 III.A. Gene Therapy 989 III.B. Viral Vectors 989 III.C. Nonvi ral Vectors 991 111.D. Cell-based Gene Therapy 991 III.E. Nanofibers and Other Synthetic Matrices 992 IV. Future View 992 References 993 Index 11
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title_auth Heart development and regeneration
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title_short Heart development and regeneration
title_sort heart development and regeneration
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