Moody Principles of Developmental Genetics

2. Auflage 2014
ISBN: 978-0-12-405923-8
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, 784 Seiten

Providing expert coverage of all major events in early embryogenesis and the organogenesis of specific systems, and supplemented with representative clinical syndromes, Principles of Developmental Genetics, Second Edition discusses the processes of normal development in embryonic and prenatal animals, including humans. The new edition of this classic work supports clinical researchers developing future therapies with its all-new coverage of systems biology, stem cell biology, new technologies, and clinical disorders. A crystal-clear layout, exceptional full-color design, and bulleted summaries of major takeaways and clinical pathways assist comprehension and readability of the highly complex content. - All-new coverage of systems biology and stem cell biology in context of evolving technologies places the work squarely on the modern sciences - Chapters are complemented with a bulleted summary for easy digestion of the major points, with a clinical summary for therapeutic application - Clinical highlights provides a bridge between basic developmental biology and clinical sciences in embryonic and prenatal syndromes

Autoren/Hrsg.

Moody, Sally A.

Inhaltsverzeichnis

1;Front
Cover;1
2;Principles of Developmental Genetics;4
3;Copyright;5
4;Contents;6
5;Preface;18
5.1;Developmental Genetics: An Historical Perspective;18
5.2;RECOMMENDED RESOURCES;19
6;Contributors;20
7;Section I - Emerging Technologies
and Systems Biology;24
7.1;Chapter 1 - Generating Diversity and Specificity through Developmental Cell Signaling;26
7.1.1;SUMMARY;27
7.1.2;1.1 INTRODUCTION;28
7.1.3;1.2 IDENTIFICATION OF SIGNALING PATHWAY COMPONENTS;31
7.1.4;1.3 FUNCTIONAL DIVERSIFICATION OF RELATED SIGNALING PROTEINS;38
7.1.5;1.4 ROLES OF CYTOPLASMIC EXTENSIONS IN CELL SIGNALING;39
7.1.6;1.5 FORMATION AND INTERPRETATION OF SIGNALING GRADIENTS;42
7.1.7;1.6 TRANSCRIPTIONAL REGULATION BY DEVELOPMENTAL CELL SIGNALING PATHWAYS;47
7.1.8;1.7 TRANSCRIPTION-INDEPENDENT RESPONSES TO CELL SIGNALING;49
7.1.9;1.8 ROLES OF COMPUTATIONAL BIOLOGY IN DEVELOPMENTAL CELL SIGNALING STUDIES;49
7.1.10;1.9 CLOSING REMARKS;50
7.1.11;1.10 CLINICAL RELEVANCE: DEVELOPMENTAL CELL SIGNALING AND HUMAN DISEASE;50
7.1.12;ACKNOWLEDGMENTS;51
7.1.13;REFERENCES;51
7.2;Chapter 2 - Applications of Deep Sequencing to Developmental Systems;60
7.2.1;SUMMARY;60
7.2.2;2.1 INTRODUCTION;60
7.2.3;2.2 USING RNA-SEQ TO MAP AND QUANTIFY TRANSCRIPTS;61
7.2.4;2.3 CHROMATIN IMMUNOPRECIPITATION FOR IDENTIFYING PROTEIN-DNA INTERACTIONS;63
7.2.5;2.4 DNASE I HYPERSENSITIVE SITE MAPPING TO IDENTIFY CIS-REGULATORY REGIONS;65
7.2.6;2.5 INTERACTIONS AT A DISTANCE;67
7.2.7;2.6 PROSPECTS;67
7.2.8;2.7 CLINICAL RELEVANCE;69
7.2.9;RECOMMENDED RESOURCES;70
7.2.10;REFERENCES;70
7.3;Chapter 3 - Using Mutagenesis in Mice for Developmental Gene Discovery;72
7.3.1;SUMMARY;72
7.3.2;3.1 USE OF ENU AS A MUTAGEN;72
7.3.3;3.2 ENU-INDUCED MUTATIONS IN MICE;74
7.3.4;3.3 ENU-INDUCED MUTATIONS AFFECTING DEVELOPMENT;75
7.3.5;3.4 IDENTIFICATION OF MODIFIER LOCI;77
7.3.6;3.5 CLINICAL RELEVANCE;79
7.3.7;RECOMMENDED RESOURCES;79
7.3.8;REFERENCES;79
7.4;Chapter 4 - Chemical Approaches to Controlling Cell Fate;82
7.4.1;SUMMARY;82
7.4.2;4.1 INTRODUCTION;83
7.4.3;4.2 CHEMICAL APPROACHES TO CONTROLLING CELL FATE;83
7.4.4;4.3 CLINICAL RELEVANCE;96
7.4.5;ACKNOWLEDGMENT/GRANT SUPPORT;96
7.4.6;RECOMMENDED RESOURCES;96
7.4.7;Web sites;96
7.4.8;Reviews;97
7.4.9;REFERENCES;97
7.5;Chapter 5 - BMP Signaling and Stem Cell Self-Renewal in the Drosophila Ovary;100
7.5.1;SUMMARY;100
7.5.2;5.1 INTRODUCTION;101
7.5.3;5.2 THE DROSOPHILA OVARY;101
7.5.4;5.3 THE BMP SIGNALING PATHWAY;103
7.5.5;5.4 REGULATION OF BMP SIGNALING BY EXTRINSIC FACTORS;105
7.5.6;5.5 REGULATION OF BMP SIGNALING BY INTRINSIC FACTORS;109
7.5.7;5.6 ADDITIONAL REGULATORS;111
7.5.8;5.7 SELECTED TOPICS;112
7.5.9;5.8 BMP SIGNALING AND STEM CELL HOMEOSTASIS IN VERTEBRATES;114
7.5.10;5.9 CONCLUSIONS;115
7.5.11;5.10 CLINICAL RELEVANCE;115
7.5.12;RECOMMENDED RESOURCES;115
7.5.13;Publications;115
7.5.14;Websites;115
7.5.15;REFERENCES;115
7.6;Chapter 6 - Genomic Analyses of Neural Stem Cells;120
7.6.1;SUMMARY;120
7.6.2;6.1 INTRODUCTION;121
7.6.3;6.2 THE IMPORTANCE OF GLOBAL ANALYSIS AND CAVEATS WHEN COMPARING CELL SAMPLES;121
7.6.4;6.3 THE USE OF A REFERENCE STANDARD;123
7.6.5;6.4 EPIGENETIC MODULATION;125
7.6.6;6.5 MICRORNA;125
7.6.7;6.6 MITOCHONDRIAL SEQUENCING;126
7.6.8;6.7 TRANSCRIPTOME MAPPING;126
7.6.9;6.8 DATA MINING: CHROMOSOME MAPPING, PATHWAY ANALYSIS, DATA REPRESENTATION;126
7.6.10;6.9 GENERAL OBSERVATIONS ABOUT THE PROPERTIES OF NEURAL STEM CELLS;128
7.6.11;6.10 SPECIES DIFFERENCES;129
7.6.12;6.11 LACK OF A “STEMNESS” PHENOTYPE;131
7.6.13;6.12 ALLELIC VARIABILITY;131
7.6.14;6.13 AGE DEPENDENT CHANGES IN NSCS;131
7.6.15;6.14 CANCER STEM CELLS;132
7.6.16;6.15 CONCLUSIONS;132
7.6.17;6.16 CLINICAL RELEVANCE;132
7.6.18;ACKNOWLEDGMENT;133
7.6.19;RECOMMENDED RESOURCES;133
7.6.20;Reviews;133
7.6.21;Websites;133
7.6.22;REFERENCES;133
7.7;Chapter 7 - Genomic and Evolutionary Insights into Chordate Origins;138
7.7.1;SUMMARY;139
7.7.2;7.1 INTRODUCTION;139
7.7.3;7.2 HOX GENE CLUSTER ORGANIZATION AND EXPRESSION IN DEUTEROSTOMES: ANTERIOR-POSTERIOR AXIS DEVELOPMENT;142
7.7.4;7.3 PHARYNGEAL GILLS AND GILL BAR DEVELOPMENT;142
7.7.5;7.4 THE POST-ANAL TAIL AND THE ENDOSTYLE OF HEMICHORDATES: GENE EXPRESSION STUDIES;143
7.7.6;7.5 THE CENTRAL NERVOUS SYSTEM AND THE DORSAL-VENTRAL INVERSION HYPOTHESIS;144
7.7.7;7.6 EVIDENCE FOR THE HEMICHORDATE STOMOCHORD HOMOLOGY TO CHORDATE NOTOCHORD;145
7.7.8;7.7 THE EVOLUTION OF PLACODES AND THE NEURAL CREST IN CHORDATES;146
7.7.9;7.8 STEM CELLS AND REGENERATION IN HEMICHORDATES;146
7.7.10;7.9 SUMMARY AND CONCLUSIONS;148
7.7.11;7.10 CLINICAL RELEVANCE;148
7.7.12;ACKNOWLEDGMENTS;148
7.7.13;RECOMMENDED RESOURCES;148
7.7.14;REFERENCES;149
8;Section II -
Early Embryology andMorphogenesis;152
8.1;Chapter 8 - Signaling Cascades, Gradients, and Gene Networks in Dorsal/Ventral Patterning;154
8.1.1;SUMMARY;154
8.1.2;8.1 INTRODUCTION;155
8.1.3;8.2 AP AND DV POLARITY IS SPECIFIED IN THE DEVELOPING OVARIOLE;156
8.1.4;8.3 FROM THE OOCYTE TO THE FERTILIZED EGG: FORMATION OF THE DL NUCLEAR CONCENTRATION GRADIENT;157
8.1.5;8.4 DPP/SOG ACTIVITY GRADIENTS ARE RESPONSIBLE FOR FURTHER PATTERNING OF THE DV AXIS;163
8.1.6;8.5 THE DV REGULATORY NETWORK;165
8.1.7;8.6 COMPARISON OF DV PATTERNING IN DROSOPHILA AND VERTEBRATES;165
8.1.8;8.7 CLINICAL RELEVANCE;167
8.1.9;RECOMMENDED RESOURCES;171
8.1.10;Internet Resources for Exploring Drosophila Development;171
8.1.11;REFERENCES;171
8.2;Chapter 9 - Building Dimorphic Forms: The Intersection of Sex Determination and Embryonic Patterning;176
8.2.1;SUMMARY;176
8.2.2;9.1 INTRODUCTION;177
8.2.3;9.2 SEX DETERMINATION IN DROSOPHILA MELANOGASTER;177
8.2.4;9.3 SEX DETERMINATION IN MAMMALS;180
8.2.5;9.4 DIMORPHISM IN THE FLY OLFACTORY SYSTEM;182
8.2.6;9.5 INTEGRATION OF SEX DETERMINATION AND EMBRYONIC PATTERN FORMATION;184
8.2.7;9.6 CLINICAL IMPLICATIONS OF SEXUAL DETERMINATION AND DIMORPHISM;188
8.2.8;9.7 CONCLUSIONS;188
8.2.9;9.8 CLINICAL RELEVANCE;189
8.2.10;ACKNOWLEDGMENTS;189
8.2.11;RECOMMENDED RESOURCES;189
8.2.12;REFERENCES;189
8.3;Chapter 10 - Formation of the Anterior-Posterior Axis in Mammals;194
8.3.1;SUMMARY;195
8.3.2;10.1 INTRODUCTION;195
8.3.3;10.2 DISCOVERY AND IMPORTANCE OF THE AVE;196
8.3.4;10.3 THE DVE IS A HETEROGENEOUS AND DYNAMIC CELL POPULATION, WHICH FORMS AFTER THE PROXIMO-DISTAL REGIONALIZATION OF THE VE;198
8.3.5;10.4 MECHANISMS OF DVE CELL MOVEMENT;201
8.3.6;10.5 EVOLUTIONARY PERSPECTIVE;205
8.3.7;10.6 CONCLUSIONS;206
8.3.8;10.7 CLINICAL RELEVANCE;206
8.3.9;ACKNOWLEDGMENTS;206
8.3.10;RECOMMENDED RESOURCES;206
8.3.11;REFERENCES;207
8.4;Chapter 11 - Early Development of Epidermis and Neural Tissue;212
8.4.1;SUMMARY;212
8.4.2;11.1 INTRODUCTION;212
8.4.3;11.2 SPECIFICATION OF ECTODERM AND MESENDODERM BY MUTUALLY ANTAGONISTIC FACTORS;213
8.4.4;11.3 SPECIFICATION OF EPIDERMIS AND NEURAL TISSUE;214
8.4.5;11.4 ECTODERMAL CELL TYPE SPECIFICATION AND CELL POLARITY;219
8.4.6;11.5 CLINICAL RELEVANCE;222
8.4.7;ACKNOWLEDGMENTS;222
8.4.8;RECOMMENDED RESOURCES;222
8.4.9;REFERENCES;222
8.5;Chapter 12 - Taking the Middle Road: Vertebrate Mesoderm Formation and the Blastula-Gastrula Transition;226
8.5.1;SUMMARY;227
8.5.2;12.1 THE DISCOVERY OF MESODERM AND GERM LAYERS;227
8.5.3;12.2 GERM LAYER PHYLOGENY;227
8.5.4;12.3 MESODERM’S FOSSIL RECORD;228
8.5.5;12.4 EMBRYONIC ORGANIZERS AND INDUCTION;229
8.5.6;12.5 CELL LINEAGE TRACING;231
8.5.7;12.6 THE BLASTULA-GASTRULA TRANSITION IN VERTEBRATES;231
8.5.8;12.7 THE CRYPTIC HOMOLOGY OF VERTEBRATE FATE MAPS;232
8.5.9;12.8 EXCEPTIONS TO PRESUMED CELL LINEAGE RESTRICTIONS;233
8.5.10;12.9 BEYOND THE BLASTULA-GASTRULA TRANSITION: CAUDAL MESODERM AND THE LEFT-RIGHT AXIS;234
8.5.11;12.11 A GENE REGULATORY NETWORK VIEW OF DEVELOPMENT;236
8.5.12;12.12 GRNS OF VERTEBRATE MESODERM FORMATION;238
8.5.13;12.13 MATERNAL ACTIVATION OF NODAL SIGNALING: X. LAEVIS AND ZEBRAFISH;239
8.5.14;12.14 ZYGOTIC REGULATION OF NODAL SIGNALING: CHICK AND MOUSE;240
8.5.15;12.15 ESTABLISHING T EXPRESSION;241
8.5.16;12.16 ESTABLISHING HOMOGENOUS CELLULAR FIELDS;242
8.5.17;12.17 THE SMO PROXIMODISTAL AXIS;242
8.5.18;12.18 SEPARATING MESENDODERM FROM ECTODERM;243
8.5.19;12.19 SEPARATING MESODERM FROM ENDODERM;244
8.5.20;12.20 EARLY ZYGOTIC GENES ARE POISED FOR ACTION;244
8.5.21;12.21 THE PHYLOTYPIC EGG TIMER;245
8.5.22;12.22 MESODERM SPECIFICATION DEFECTS IN HUMANS;246
8.5.23;12.23 HUMAN GENE VARIANTS ASSOCIATED WITH MESODERM SPECIFICATION DEFECTS;247
8.5.24;12.24 IMPLICATIONS OF A PAN-N-M CAUDAL AXIS;248
8.5.25;12.25 CONCLUDING REMARKS;249
8.5.26;12.26 CLINICAL RELEVANCE;249
8.5.27;ACKNOWLEDGMENTS;250
8.5.28;RECOMMEND RESOURCES;250
8.5.29;Animal Model Databases;250
8.5.30;BioTapestry Software;250
8.5.31;Reading;250
8.5.32;Rare Biomedical Texts;250
8.5.33;REFERENCES;250
8.6;Chapter 13 - Vertebrate Endoderm Formation;260
8.6.1;SUMMARY;260
8.6.2;13.1 INTRODUCTION;261
8.6.3;13.2 OVERVIEW OF ENDODERM MORPHOGENESIS IN VERTEBRATES;262
8.6.4;13.3 MOLECULAR MECHANISMS OF ENDODERM DEVELOPMENT;264
8.6.5;13.4 ENDODERM GRN TRANSCRIPTION FACTORS;266
8.6.6;13.5 MODULATION OF THE ENDODERM GRN BY OTHER SIGNALING PATHWAYS;268
8.6.7;13.6 HUMAN ENDODERM DIFFERENTIATION IN PLURIPOTENT STEM CELLS;269
8.6.8;13.7 CLINICAL RELEVANCE;270
8.6.9;ACKNOWLEDGMENTS;270
8.6.10;RECOMMENDED RESOURCES;270
8.6.11;REFERENCES;270
8.7;Chapter 14 - Epithelial Branching: Mechanisms of Patterning and Self-Organization;278
8.7.1;SUMMARY;278
8.7.2;14.1 INTRODUCTION: THE IMPORTANCE OF EPITHELIAL BRANCHING TO ORGANOGENESIS;278
8.7.3;14.2 TYPES AND SCALES OF BRANCHING MORPHOGENESIS;279
8.7.4;14.3 THE ROLE OF GENETICS IN STUDYING MECHANISMS OF BRANCHING MORPHOGENESIS;280
8.7.5;14.4 THE PROBLEMS: WHAT MOST NEEDS TO BE EXPLAINED;280
8.7.6;14.5 SYMMETRY-BREAKING: WHY DO EPITHELIA BRANCH RATHER THAN JUST BALLOON?;281
8.7.7;14.6 TIPS AND STALKS;281
8.7.8;14.7 PATTERNING: HOW TO MAKE A TREE NOT A TANGLE;283
8.7.9;14.8 IMPOSING SUBTLETY: MAKING ORGAN-SPECIFIC PATTERNS;284
8.7.10;14.9 CLINICAL RELEVANCE;285
8.7.11;RECOMMENDED RESOURCES;285
8.7.12;REFERENCES;285
8.8;Chapter 15 - Lessons from the Zebrafish Lateral Line System;288
8.8.1;SUMMARY;289
8.8.2;15.1 INTRODUCTION;289
8.8.3;15.2 EMERGENCE OF THE PLL SYSTEM;290
8.8.4;15.3 MORPHOGENESIS AND SEQUENTIAL FORMATION OF PROTONEUROMASTS IN THE PLLP;290
8.8.5;15.4 ESTABLISHMENT OF POLARIZED WNT AND FGF SIGNALING SYSTEMS IN THE PLLP;292
8.8.6;15.5 SPECIFICATION OF A CENTRAL HAIR CELL PROGENITOR BY LATERAL INHIBITION MEDIATED BY NOTCH SIGNALING;293
8.8.7;15.6 THE HAIR CELL PROGENITOR BECOMES A NEW LOCALIZED SOURCE OF FGF;294
8.8.8;15.7 NOTCH SIGNALING – AN ESSENTIAL NODE IN THE SELF-ORGANIZATION OF THE PLLP;295
8.8.9;15.8 PERIODIC FORMATION OF PROTONEUROMASTS;295
8.8.10;15.9 TERMINATION OF THE PLLP SYSTEM;296
8.8.11;15.10 POLARIZED MIGRATION OF THE PLLP ALONG A PATH DEFINED BY CHEMOKINE SIGNALS;296
8.8.12;15.11 REGULATION OF NEUROMAST SPACING;298
8.8.13;15.12 CONCLUSIONS;298
8.8.14;15.13 CLINICAL RELEVANCE;299
8.8.15;RECOMMENDED RESOURCES;299
8.8.16;REFERENCES;299
8.8.17;NOTE ADDED IN PROOF;302
9;Section III -
Organogenesis;304
9.1;Chapter 16 - Neural Cell Fate Determination;306
9.1.1;SUMMARY;306
9.1.2;16.1 INTRODUCTION;307
9.1.3;16.2 FUNDAMENTALS OF NEUROGENESIS;307
9.1.4;16.3 THE GENERATION OF SPECIFIC CELL TYPES WITHIN THE VERTEBRATE NERVOUS SYSTEM: SPINAL CORD DEVELOPMENT;308
9.1.5;16.4 COMMON THEMES IN CNS DEVELOPMENT;311
9.1.6;16.5 POSTMITOTIC REFINEMENT OF SUBTYPE IDENTITY;312
9.1.7;16.6 APPLYING DEVELOPMENTAL PRINCIPLES TO STEM CELL RESEARCH: DIRECTED DIFFERENTIATION FROM PLURIPOTENT STEM CELLS;312
9.1.8;16.7 USING TRANSCRIPTION FACTOR CODES TO DIRECTLY SPECIFY CELL FATE;314
9.1.9;16.8 MODELING HUMAN NEUROLOGICAL DISORDERS AND DISEASES;315
9.1.10;CLINICAL RELEVANCE;316
9.1.11;RECOMMENDED RESOURCES;316
9.1.12;REFERENCES;316
9.2;Chapter 17 - Retinal Development;320
9.2.1;SUMMARY;320
9.2.2;17.1 INTRODUCTION;321
9.2.3;17.2 EYE FIELD SPECIFICATION;321
9.2.4;17.3 OPTIC VESICLE AND CUP FORMATION;324
9.2.5;17.4 RETINAL PROGENITOR PROLIFERATION;326
9.2.6;17.5 RETINOGENESIS;327
9.2.7;17.6 ADULT RETINAL STEM CELLS AND RETINAL REGENERATION;329
9.2.8;17.7 RETINAL STEM/PROGENITOR CELLS FOR RETINAL REPAIR;331
9.2.9;17.8 CONCLUSIONS AND FUTURE DIRECTIONS;332
9.2.10;17.9 CLINICAL RELEVANCE;333
9.2.11;RECOMMENDED RESOURCES;333
9.2.12;REFERENCES;333
9.3;Chapter 18 - Neural Crest Determination and Migration;338
9.3.1;SUMMARY;338
9.3.2;18.1 INTRODUCTION;339
9.3.3;18.2 TECHNIQUES TO IDENTIFY NEURAL CREST DEVELOPMENT;340
9.3.4;18.3 SPECIFICATION OF NEURAL CREST CELLS;341
9.3.5;18.4 NEURAL CREST CELL MIGRATION;346
9.3.6;18.5 HUMAN PATHOLOGIES;349
9.3.7;18.6 CLINICAL RELEVANCE;350
9.3.8;ACKNOWLEDGMENTS;350
9.3.9;RECOMMENDED RESOURCES;350
9.3.10;REFERENCES;350
9.4;Chapter 19 - Development of the Pre-Placodal Ectoderm and Cranial Sensory Placodes;354
9.4.1;SUMMARY;354
9.4.2;19.1 INTRODUCTION;355
9.4.3;19.2 CRANIAL SENSORY PLACODES GIVE RISE TO DIVERSE STRUCTURES;355
9.4.4;19.3 SPECIFICATION OF THE PRE-PLACODAL ECTODERM;357
9.4.5;19.4 GENES THAT SPECIFY PRE-PLACODAL ECTODERM FATE;361
9.4.6;19.5 MAINTAINING THE BOUNDARIES OF THE PRE-PLACODAL ECTODERM;366
9.4.7;19.6 PLACODE IDENTITY;367
9.4.8;19.7 REGULATION OF PLACODE-DERIVED SENSORY NEURON DIFFERENTIATION;369
9.4.9;19.8 FUTURE DIRECTIONS;371
9.4.10;19.9 CLINICAL RELEVANCE;371
9.4.11;ACKNOWLEDGMENTS;372
9.4.12;RECOMMENDED RESOURCES;372
9.4.13;REFERENCES;372
9.5;Chapter 20 - Building the Olfactory System: Morphogenesis and Stem Cell Specification in the Olfactory Epithelium and Olfactory Bulb;380
9.5.1;Morphogenesis and Stem Cell Specification in the Olfactory Epithelium and Olfactory Bulb;380
9.5.2;SUMMARY;380
9.5.3;20.1 INTRODUCTION;381
9.5.4;20.2 THE INITIAL DEVELOPMENT OF THE OLFACTORY PATHWAY;382
9.5.5;20.3 OE INDUCTION: NON-AXIAL MESENCHYMAL/EPITHELIAL INTERACTIONS DRIVE DIFFERENTIATION;383
9.5.6;20.4 OB INDUCTION: PARALLEL M/E REGULATION OF INITIAL MORPHOGENESIS;386
9.5.7;20.5 STEM CELLS, CELL LINEAGES AND NEURONAL SPECIFICATION IN THE OE;389
9.5.8;20.6 CELL LINEAGES, MIGRATION AND NEURONAL SPECIFICATION IN THE DEVELOPING AND ADULT OB;390
9.5.9;20.7 OLFACTORY PATHWAY DEVELOPMENT BEYOND MORPHOGENESIS, STEM CELLS AND NEURONAL SPECIFICATION;392
9.5.10;20.8 PERSPECTIVE;394
9.5.11;20.9 CLINICAL RELEVANCE;394
9.5.12;RECOMMENDED RESOURCES;394
9.5.13;For information about the functional organization of the olfactory system;394
9.5.14;For information about adult neurogenesis in the olfactory pathway;394
9.5.15;For information about odorant receptor-selective mapping in the olfactory pathway;394
9.5.16;REFERENCES;394
9.6;Chapter 21 - Development of the Inner Ear;400
9.6.1;SUMMARY;400
9.6.2;21.1 INTRODUCTION;401
9.6.3;21.2 ANATOMY OF THE INNER EAR;401
9.6.4;21.3 SPECIFICATION OF NEURAL AND SENSORY FATES: A COMMON ORIGIN FOR NEURONAL AND PROSENSORY CELLS;403
9.6.5;21.4 DEVELOPMENT OF THE SEMICIRCULAR CANALS AND CRISTAE;404
9.6.6;21.5 DEVELOPMENT OF THE COCHLEAR DUCT AND ORGAN OF CORTI;405
9.6.7;CONCLUSIONS;410
9.6.8;CLINICAL RELEVANCE;410
9.6.9;REFERENCES;410
9.7;Chapter 22 - Molecular Genetics of Tooth Development;416
9.7.1;SUMMARY;416
9.7.2;22.1 INTRODUCTION;417
9.7.3;22.2 DEVELOPMENTAL ANATOMY;417
9.7.4;22.3 GENE EXPRESSION PATTERN DATABASES;418
9.7.5;22.4 THE DISRUPTION OF SIGNALING PATHWAYS ARRESTS MOUSE TOOTH DEVELOPMENT;419
9.7.6;22.5 THE GENETIC BASIS OF HUMAN TOOTH AGENESIS;420
9.7.7;22.6 DENTAL PLACODES AND THE PATHOGENESIS OF ECTODERMAL DYSPLASIA SYNDROMES;420
9.7.8;22.7 ENAMEL KNOTS, TOOTH SHAPES, AND THE FINE-TUNING OF SIGNAL PATHWAYS;422
9.7.9;22.8 THE GENETIC BASIS OF TOOTH REPLACEMENT;423
9.7.10;22.9 THE DEVELOPMENTAL GENETICS OF DENTIN AND ENAMEL FORMATION;424
9.7.11;22.10 CLINICAL RELEVANCE;425
9.7.12;RECOMMENDED RESOURCES;425
9.7.13;REFERENCES;425
9.8;Chapter 23 - Early Heart Development;430
9.8.1;SUMMARY;430
9.8.2;23.1 INTRODUCTION;431
9.8.3;23.2 EMBRYOLOGY OF HEART DEVELOPMENT;431
9.8.4;23.3 MULTIPLE SIGNALING PATHWAYS ARE INVOLVED IN EARLY CARDIOGENESIS;433
9.8.5;23.4 TRANSCRIPTIONAL REGULATION OF EARLY HEART DEVELOPMENT;436
9.8.6;23.5 PROGRAMMING AND REPROGRAMMING OF CELLS TOWARDS A CARDIAC FATE;439
9.8.7;23.6 CONCLUSIONS;439
9.8.8;23.7 CLINICAL SIGNIFICANCE;439
9.8.9;ACKNOWLEDGMENTS;440
9.8.10;RECOMMENDED RESOURCES;440
9.8.11;REFERENCES;440
9.9;Chapter 24 - Blood Vessel Formation;444
9.9.1;SUMMARY;445
9.9.2;24.1 INTRODUCTION;445
9.9.3;24.2 EMERGENCE OF THE BLOOD VASCULAR SYSTEM;445
9.9.4;24.3 ARTERIAL-VENOUS DIFFERENTIATION;451
9.9.5;24.4 EMERGENCE OF THE LYMPHATIC SYSTEM;456
9.9.6;24.5 PATTERNING OF THE DEVELOPING VASCULATURE;459
9.9.7;24.6 CONCLUDING REMARKS;464
9.9.8;24.7 CLINICAL RELEVANCE;464
9.9.9;ACKNOWLEDGMENTS;464
9.9.10;REFERENCES;465
9.10;Chapter 25 - Blood Induction and Embryonic Formation;474
9.10.1;SUMMARY;474
9.10.2;25.1 INTRODUCTION;475
9.10.3;25.2 ORIGIN OF BLOOD CELLS DURING EMBRYOGENESIS;475
9.10.4;25.3 TRANSCRIPTIONAL REGULATION OF BLOOD DEVELOPMENT;479
9.10.5;25.4 THERAPEUTIC USE OF HSCS;483
9.10.6;25.5 CLINICAL RELEVANCE;483
9.10.7;RECOMMENDED RESOURCES;484
9.10.8;REFERENCES;484
9.11;Chapter 26 - How to Build a Kidney;492
9.11.1;SUMMARY;492
9.11.2;26.1 INTRODUCTION;492
9.11.3;26.2 THE NEPHRIC DUCT;495
9.11.4;26.3 NEPHRON SEGMENTATION;499
9.11.5;26.4 KIDNEY STEM CELLS?;503
9.11.6;26.5 SUMMARY AND FUTURE DIRECTIONS;504
9.11.7;CLINICAL RELEVANCE;504
9.11.8;ACKNOWLEDGMENTS;505
9.11.9;RECOMMENDED RESOURCES;505
9.11.10;REFERENCES;505
9.12;Chapter 27 - Development of the Genital System;510
9.12.1;SUMMARY;511
9.12.2;27.1 INTRODUCTION;511
9.12.3;27.2 GENETIC SEX DETERMINATION;511
9.12.4;27.3 GONADAL DIFFERENTIATION;514
9.12.5;27.4 DEVELOPMENT OF THE GENITAL DUCTS;519
9.12.6;27.5 DEVELOPMENT OF THE EXTERNAL GENITALIA;522
9.12.7;27.6 MALFORMATIONS OF THE GENITAL SYSTEM;523
9.12.8;27.7 CONCLUSION;525
9.12.9;RECOMMENDED RESOURCES;525
9.12.10;REFERENCES;525
9.13;Chapter 28 - Skeletal Development;528
9.13.1;SUMMARY;528
9.13.2;28.1 INTRODUCTION;529
9.13.3;28.2 THE APPENDICULAR SKELETON;529
9.13.4;28.3 AXIAL SKELETON;538
9.13.5;28.4 CONCLUSION;547
9.13.6;28.5 CLINICAL RELEVANCE;548
9.13.7;ACKNOWLEDGMENTS;548
9.13.8;RECOMMENDED RESOURCES;548
9.13.9;Chondrogenesis/endochondral ossification;548
9.13.10;Somitogenesis;548
9.13.11;REFERENCES;548
9.14;Chapter 29 - Formation of Vertebrate Limbs;554
9.14.1;SUMMARY;554
9.14.2;29.1 INTRODUCTION;555
9.14.3;29.2 LIMB INITIATION;555
9.14.4;29.3 LIMB BUD OUTGROWTH AND PATTERNING;557
9.14.5;29.4 LIMB DEVELOPMENT AND DISEASES;562
9.14.6;29.5 CONCLUSIONS AND PERSPECTIVES;563
9.14.7;29.6 CLINICAL RELEVANCE;564
9.14.8;RECOMMENDED RESOURCES;564
9.14.9;REFERENCES;564
9.15;Chapter 30 - Patterning the Embryonic Endoderm into Presumptive Organ Domains;568
9.15.1;SUMMARY;569
9.15.2;30.1 INTRODUCTION;569
9.15.3;30.2 FATE MAP OF THE EMBRYONIC ENDODERM;570
9.15.4;30.3 GENE EXPRESSION DOMAINS PREDICT AND DETERMINE ENDODERM ORGAN PRIMORDIA;573
9.15.5;30.4 TRANSLATIONAL EMBRYOLOGY: THE IMPACT OF EMBRYONIC STUDIES ON HUMAN HEALTH;582
9.15.6;CLINICAL RELEVANCE;583
9.15.7;ACKNOWLEDGMENTS;583
9.15.8;REFERENCES;583
9.16;Chapter 31 - Pancreas Development and Regeneration;588
9.16.1;SUMMARY;589
9.16.2;31.1 INTRODUCTION;589
9.16.3;31.2 THE INITIAL STAGES OF PANCREATIC BUD FORMATION;590
9.16.4;31.3 INDUCTIVE INTERACTIONS DURING PANCREAS DEVELOPMENT;592
9.16.5;31.4 GENES THAT AFFECT PANCREATIC BUD DEVELOPMENT;593
9.16.6;31.5 GENES THAT AFFECT THE DIFFERENTIATION OF PARTICULAR PANCREATIC CELL TYPES;596
9.16.7;31.6 GENERATING ISLETS/.-CELLS FROM STEM OR PROGENITOR CELLS;603
9.16.8;31.7 CLINICAL RELEVANCE;604
9.16.9;ACKNOWLEDGMENTS;604
9.16.10;REFERENCES;604
10;Section IV -
Selected Clinical Problems;614
10.1;Chapter 32 - Diaphragmatic Embryogenesis and Human Congenital Diaphragmatic Defects;616
10.1.1;SUMMARY;617
10.1.2;32.1 INTRODUCTION;617
10.1.3;32.2 DIAPHRAGMATIC ANATOMY;618
10.1.4;32.3 DIAPHRAGMATIC DEVELOPMENT;620
10.1.5;32.4 GENETICS OF HUMAN CONGENITAL DIAPHRAGMATIC DEFECTS;624
10.1.6;32.5 CARDIOPULMONARY DEVELOPMENT AND THE DIAPHRAGM;625
10.1.7;CONCLUSIONS;626
10.1.8;CLINICAL RELEVANCE;626
10.1.9;REFERENCES;627
10.2;Chapter 33 - Genetic and Developmental Basis of Congenital Cardiovascular Malformations;630
10.2.1;SUMMARY;631
10.2.2;33.1 UNDERSTANDING CONGENITAL HEART DEFECTS IN THE CONTEXT OF NORMAL CARDIAC DEVELOPMENT;631
10.2.3;33.2 HEART TUBE AND CARDIAC LOOPING;640
10.2.4;33.3 FORMATION OF THE ATRIOVENTRICULAR CANAL;642
10.2.5;33.4 TARGETED GROWTH OF THE PULMONARY VEINS;644
10.2.6;33.5 ATRIAL AND VENTRICULAR SEPTATION;645
10.2.7;33.6 VALVULOGENESIS AND OUTFLOW TRACT DEVELOPMENT;646
10.2.8;33.7 INTRACARDIAC CONDUCTION SYSTEM;649
10.2.9;33.8 CLINICAL RELEVANCE;649
10.2.10;RECOMMENDED RESOURCES;650
10.2.11;REFERENCES;650
10.3;Chapter 34 - T-Box Genes and Developmental Anomalies;658
10.3.1;SUMMARY;658
10.3.2;34.1 T-BOX GENES: TRANSCRIPTION FACTOR GENES WITH MANY DEVELOPMENTAL ROLES;659
10.3.3;34.2 DNA BINDING AND TRANSCRIPTIONAL REGULATION BY T-BOX PROTEINS;660
10.3.4;34.3 HUMAN SYNDROMES AND MOUSE MODELS;661
10.3.5;34.4 FUTURE DIRECTIONS;670
10.3.6;CLINICAL RELEVANCE;670
10.3.7;ACKNOWLEDGMENTS;670
10.3.8;RECOMMENDED RESOURCES;670
10.3.9;REFERENCES;671
10.4;Chapter 35 - Craniofacial Syndromes: Etiology, Impact and Treatment;676
10.4.1;SUMMARY;677
10.4.2;35.1 INTRODUCTION;677
10.4.3;35.2 FIRST ARCH DERIVED STRUCTURES;678
10.4.4;35.3 MIDFACE;682
10.4.5;35.4 CRANIAL VAULT;689
10.4.6;35.5 Conclusions;693
10.4.7;HISTORY, FUTURE AND OPTIONS FOR PHARMACOLOGICAL TREATMENT OF CRANIOFACIAL SYNDROMES;693
10.4.8;35.6 CLINICAL RELEVANCE;694
10.4.9;RECOMMENDED RESOURCES;694
10.4.10;REFERENCES;694
10.5;Chapter 36 - 22q11 Deletion Syndrome: Copy Number Variations and Development;700
10.5.1;SUMMARY;700
10.5.2;36.1 22Q11DS IS A GENOMIC DISORDER WITH WIDESPREAD CONSEQUENCES FOR DEVELOPMENT;701
10.5.3;36.2 22Q11DS AS VIEWED FROM A DEVELOPMENTAL PERSPECTIVE;705
10.5.4;36.3 GENES AND PHENOTYPES: 22Q11DS AS A PROTOTYPE GENOMIC DISEASE;714
10.5.5;36.4 CLINICAL RELEVANCE;715
10.5.6;ACKNOWLEDGEMENTS;715
10.5.7;REFERENCES;715
10.6;Chapter 37 - Neural Tube Defects;720
10.6.1;SUMMARY;720
10.6.2;37.1 INTRODUCTION;721
10.6.3;37.2 DISCUSSION;721
10.6.4;37.3 FUTURE DIRECTIONS;734
10.6.5;37.4 CLINICAL RELEVANCE;734
10.6.6;RECOMMENDED RESOURCES;734
10.6.7;REFERENCES;734
11;Glossary;746
12;Index;756

Leseproben

Preface
Developmental Genetics: An Historical Perspective Sally A. Moody,     Department of Anatomy and Regenerative Biology, The George Washington University, School of Medicine and Health Sciences Washington DC, DC, USA The ability of researchers to answer experimental questions greatly depends on the available technologies. New technologies lead to novel observations and field-changing discoveries, and influence the types of questions that can be asked. Today’s recently available technologies include sequencing and analyzing the genomes of human and model organisms, genome-wide expression and epigenetic profiling, and high-throughput screening. The information provided by these approaches enables us to begin to understand the complexity of many biological processes through the elucidation of gene regulatory networks, signaling pathway networks, and epigenetic modifications. This book describes many lines of research that are being impacted by these new technologies, including developmental genetics and the related fields of clinical genetics, birth defects research, stem cell biology, regenerative medicine, and evolutionary biology. The field of developmental genetics, or the study of how genes influence the developmental processes of an organism, has been influenced by new technologies and by interactions with other fields of study throughout its history. The concept of a genetic basis of development began in “modern” times at the intersection of descriptive embryology and cytology. Modern histological techniques were developed in the mid-19th century, largely by Wilhelm His so that he could study cell division in the neural tube, which enabled visualization of the cell nucleus, chromosomes, and the discrete steps of mitosis. Theodor Boveri cleverly applied these improved microscopic techniques to transparent marine embryos to demonstrate that each parent contributes equivalent groups of chromosomes to the zygote, and that each chromosome is an independently inherited unit. Importantly, he noted that if an embryo contains the incorrect number or improper combination of chromosomes it develops abnormally. However, many early embryologists rejected the idea that development is driven by prepackaged heritable particles because it seemed too similar to the idea of “preformation”: the concept that development is driven by predetermined factors or “force” (sometimes described in rather mystical terms). Wilhelm Roux, an advocate of studying the embryo from a mechanistic point of view, was a leader in manipulating the embryo with microsurgical techniques to elucidate causes and effects between component parts (experimental embryology). By using an animal model whose embryos were large, developed externally to the mother, could be surgically manipulated with sharpened forceps, and cultured in simple salt media (i.e., amphibians), he rejected the role of predetermined factors and demonstrated the importance of external (epigenetic) influences and cell-cell interactions in regulating developmental programs. Experimental embryologists further refined their skills in dissecting small bits of tissue from the embryo, recombining them with other tissues in culture or transplanting them to ectopic regions in the embryo. This work led to the invention of tissue culture by Ross Harrison and the discovery of tissue inductions by Hans Spemann and Hilde Mangold. While experimental embryology was thriving, T. H. Morgan founded the field of Drosophila genetics. Also trained as an embryologist, Morgan was skeptical of Boveri’s idea of heritable packets, and directed his studies towards understanding the principles of inheritance. For several decades, the two fields, experimental embryology and genetics, had little impact on one another. Interestingly, however, after a few decades of study of the fruit fly, Morgan’s work supported the idea of discrete intracellular particles that directed heritable traits, which he named “genes.” Nonetheless, experimental embryology and genetics remained fairly separate fields with distinct goals and points of view. Embryologists were elucidating the interactions that are important for the development of numerous tissues and organs, whereas geneticists were focused on the fundamentals of gene inheritance, regulation of expression, and discovering the genetic code. Much of this work was carried out in non-mammalian animal models that develop external to the mother, and thus can be manipulated during during development and/or have very short life cycles. Elucidating the genetic basis of vertebrate development was delayed until new technologies in molecular biology and cloning were devised. The techniques for cloning eukaryotic genes and constructing vectors for controlling expression came from the field of bacterial and viral genetics. The rationale for and techniques of mutagenizing the entire genome and screening for developmental abnormalities came from the classical genetic studies in the fly and nematode. Important regulatory genes were discovered in these invertebrates, and their counterparts have been identified in many other animals, including mammals, by homology cloning approaches that were not common until the 1990s. Thus was born the modern field that we call developmental genetics. An important advance has been the demonstration that homologues of the genes that regulate developmental processes in invertebrates also have important developmental functions in vertebrates. The wealth of information concerning the molecular genetic processes that regulate development in various animals demonstrates that developmental programs and biological processes are highly conserved, albeit not identical, from yeast to human. Indeed, the Human Genome Project has made it possible to identify the homologues in humans, and to demonstrate that many of these regulatory genes underlie human developmental disorders, birth defects, and aspects of adult diseases in which differentiation processes go awry. Currently, researchers are studying the fundamentals of developmental processes in the appropriate animal model and screening humans for mutations in the genes identified by the basic research to be likely causative candidates. Researchers are mutagenizing vertebrate animal models and screening for mutants that resemble known human syndromes. Stem cell biologists are using the molecular genetic information discovered by from developmental biology researchers to understand how to manipulate cellular differentiation in vitro and direct pluripotent cells to desired lineages for tissue replacement therapies. This cross-fertilization of fields is also impacting concepts in evolutionary biology, leading to a better understanding of “ancestral” species and tissue anlage via homologous gene expression profiles. In recent years there have been significant technological advances in genetic, genomic, epigenetic, and protein expression analyses that are having a major impact on experimental approaches and analytical design. The intersection of developmental biology with these technologies offers a new view of developmental genetics that is only now beginning to be exploited in clinical approaches. It is this new intersection between modern developmental genetic approaches and potential clinical interventions that is the focus of this book. The book is organized into sections focused on different aspects of developmental genetics. Section I discusses the impact of new genetic and genomic technologies on development, stem cell biology, evolutionary biology, and understanding human birth defects. Section II discusses several major events in early embryogenesis, fate determination, and patterning, including cellular determinants (Boveri revisited?), gene cascades regulating embryonic axis formation, signaling molecules and transcription factors that regulate pattern formation, and the induction of the primary germ layers (ectoderm, mesoderm, and endoderm). Section III describes the morphogenetic and cellular movements that underlie the foundation of the organ systems, with a focus on the signaling cascades and transcriptional pathways that regulate organogenesis in representative systems derived from the embryonic ectoderm, mesoderm, and endoderm. These chapters illustrate how embryonic rudiments become organized into adult tissues, and how defects in these processes can result in congenital defects or disease. Each chapter demonstrates the usefulness of studying model organisms and discusses how this information applies to normal human development and clinical disorders. Several of the chapters in this section also discuss the utility of stem cells to repair damaged organs and the application of developmental genetics to the manipulation of stem cells for regenerative medicine. Section IV presents the developmental genetic underpinnings of a few selected clinical problems that commonly face pediatricians. The goal of this book is to provide a resource for understanding the critical embryonic and prenatal developmental processes that are fundamental to the normal development of animals, including humans. It highlights new technologies to be used, new questions to be answered, and the important roles that invertebrate and vertebrate animal models have had in elucidating the genetic basis of human development and disease. Developmental genetics has re-emerged from its birth a century ago as a nexus of diverse fields that are using the common language of gene sequence and function. This is influencing what questions are posed and how the answers are used. New technologies are making it relatively easy to study gene expression and regulation at single cell, tissue, and embryonic levels. The conservation between the...