Activation of Egg Metabolism in Sea Urchins 139 The polar lobe: Cell determination and axis Release of intracellular calcium ions 139 formation 182 Effects of calcium 142 Gastrulation in Snails 185 m SiDELIGHTS SPECULATIONS Rules of Evidence: "Find It R SIDELIGHTS SPECULATIONS Adaptation by Modifying Lose It move It" 1 Embryonic Cleavage 186 Fusion of genetic material 14 EARLY DEVELOPMENT IN TUNICATES 187 Internal Fertilization in Mammals 145 Tunicate Cleavage 187 Getting the gametes into the oviduct: Translocation The tunicate fate map 187 Autonomous and conditional specification of In the vicinity of the oocyte: Hyperactivation tunicate blastomeres 188 thermotaxis, and chemotaxis 148 Specification of the embryonic axes 191 Recognition at the zona pellucida 149 Gastrulation in Tunicates 19 Gamete fusion and the prevention of THE NEMATODE C ELEGANS 192 polyspermy 152 Cleavage and Axis Formation in C elegans 193 Fusion of genetic material 153 H SIDELIGHTS SPECULATIONS The Nonequivalence of Rotational cleavage of the C elegans egg 193 Mammalian Pronuclei 154 Anterior-posterior axis formation 193 Activation of the mammalian egg 155 Formation of the dorsal-ventral and right-left axes 196 Coda 155 Control of blastomere identity 197 Gastrulation in C elegans 199 Coda 200 CHAPTER 5 Early Development in Selected chaPTeR 6 Invertebrates 159 The Genetics of Axis Specification EARLY DEVELOPMENTAL PROCESSES: AN in Drosophila 203 OVERVIEW 159 Cleavage 159 EARLY DROSOPHILA DEVELOPMENT 204 From fertilization to cleavage 160 Fertilization 204 The cytoskeletal mechanisms of mitosis 161 Cleavage 204 Patterns of embryonic cleavage 162 The mid-blastula transition 205 Gastrulation 162 Gastrulation 206 Cell Specification and Axis Formation 164 GENES THAT PATTERN THE DROSOPHILA EARLY DEVELOPMENT IN SEA URCHINS 165 BODY PLAN 208 Sea Urchin Cleavage 165 Primary Axis Formation during Oogenesis 209 Blastula formation 166 Anterior-posterior polarity in the oocyte 209 Fate maps and the determination of sea urchin Dorsal-ventral patterning in the oocyte 211 blastomeres 166 Generating the Dorsal-Ventral Pattern in the Global regulatory networks and skeletogenic Embryo 213 mesenchyme specification 16 Dorsal, the ventral morphogen 213 Specification of the vegetal cells 171 Establishing a nuclear Dorsal gradient 214 Axis specification 172 Effects of the Dorsal protein gradient 214 Sea Urchin Gastrulation 172 I SIDELIGHTS SPECULATIONS The Left-Right Axis 217 Ingression of the skeletogenic mesenchyme 172 Segmentation and the Anterior-Posterior Invagination of the archenteron 176 Body plan 218 EARLY DEVELOPMENT IN SNAILS 178 Maternal gradients: Polarity regulation by oocyte Cleavage in Snail Embryos 178 cytoplasm 219 The snail fate 181 The molecular model: Protein gradients in the early ryo 219
Activation of Egg Metabolism in Sea Urchins 139 Release of intracellular calcium ions 139 Effects of calcium 142 • SIDELIGHTS & SPECULATIONS Rules of Evidence: "Find It, Lose It, Move It" 144 Fusion of genetic material 145 Internal Fertilization in Mammals 145 Getting the gametes into the oviduct: Translocation and capacitarion 145 In the vicinity of the oocyte: Hyperacrivation, thcrmotaxis, and chemo taxis 148 Recognition at the zona pellucida 149 Gamete fusion and the prevention of polyspermy 152 Fusion of genetic material 153 • SIDELIGHTS & SPECULATIONS The Nonequivalence of Mammalian Pronuclei 154 Activation of the mammalian egg 155 Coda 155 CHAPTER 5 Early Development in Selected Invertebrates 159 EARLY DEVELOPMENTAL PROCESSES: AN OVERVIEW 159 Cleavage 159 From fertilization to cleavage 160 The cytoskeletal mechanisms of mitosis 161 Patterns of embryonic cleavage 162 Gastrulation 162 Cell Specification and Axis Formation 164 EARLY DEVELOPMENT IN SEA URCHINS 165 Sea Urchin Cleavage 165 Blastula formation 166 Fate maps and the determination of sea urchin blastomeres 166 Global regulatory networks and skeletogenic mesenchyme specification 167 Specification of the vegetal cells 171 Axis specification 172 Sea Urchin Gastrulation 172 Ingression of the skeletogenic mesenchyme 172 Invagination of the archenteron 176 EARLY DEVELOPMENT IN SNAILS 178 Cleavage in Snail Embryos 178 The snail fate map 181 The polar lobe: Cell determination and axis formation 182 Gastrulation in Snails 185 • SIDELIGHTS & SPECULATIONS Adaptation by Modifying Embryonic Cleavage 186 EARLY DEVELOPMENT IN TUNICATES 187 Tunicate Cleavage 187 The tunicate fate map 187 Autonomous and conditional specification of tunicate blastomeres 188 Specification of the embryonic axes 191 Gastrulation in Tunicates 191 THE NEMATODE C. ELEGANS 192 Cleavage and Axis Formation in C. elegans 193 Rotational cleavage of the C. elegans egg 193 Anterior-posterior axis formation 193 Formation of the dorsal-ventral and right-left axes 196 Control of blastomere identity 197 Gastrulation in C. elegans 199 Coda 200 CHAPTER 6 The Genetics of Axis Specification in Drosophila 203 EARLY DROSOPHILA DEVELOPMENT 204 Fertilization 204 Cleavage 204 The mid-blastula transition 205 Gastrulation 206 GENES THAT PATTERN THE DROSOPHILA BODY PLAN 208 Primary Axis Formation during Oogenesis 209 Anterior-posterior polarity in the oocyte 209 Dorsal-ventral patterning in the oocyte 211 Generating the Dorsal-Ventral Pattern in the Embryo 213 Dorsal, the ventral morphogen 213 Establishing a nuclear Dorsal gradient 214 Effects of the Dorsal protein gradient 214 • SIDELIGHTS & SPECULATIONS The Left-Right Axis 217 Segmentation and the Anterior-Posterior Body Plan 218 Maternal gradients: Polarity regulation by oocyte cytoplasm 219 The molecular model: Protein gradients in the early embryo 219
X CONTENTS The anterior organizing center: The Bicoid and l SIDELIGHTS SPECULATIONS BMP4 and Geoffroy's Hunchback gradients 223 Lobster 267 The termimal gene group 225 The Regional Specificity of Neural Induction 267 Summarizing early anterior-posterior axis The head inducer: Wnt inhibitors 268 specification in Drosophila 226 Trunk patterning: Wnt signals and retinoic acid 270 Segmentation Genes 226 Specifying the Left-Right Axis 272 a SIDELIGHTS SPECULATIONS Segments and EARLY ZEBRAFISH DEVELOPMENT 273 Parasegments 227 Cleavage 275 The gap genes 228 The pair-rule genes 229 Gastrulation and Formation of the Germ Layers 277 The segment polarity genes 231 The Homeotic Selector Genes 234 Axis Formation in Zebrafish 278 Initiating and maintaining the patterns of homeotic Dorsal-ventral axis formation 278 gene expression 235 The fish Nieuwkoop center 281 Realisator genes 236 Anterior-posterior axis formation 282 Axes and Organ Primordia: The Cartesian ght axis formation 282 Coordinate Model 236 Coda 283 Coda 237 chaPTER 8 CHAPTER Z Birds and Mammals: Early Amphibians and Fish: Early Development and Axis Formation 287 Development and Axis Formation 241 EARLY DEVELOPMENT IN BIRDS 287 EARLY AMPHIBIAN DEVELOPMENT 242 Cleavage 287 Fertilization, Cortical Rotation, and Cleavage 242 Gastrulation of the Avian Embryo 288 Unequal radial holoblastic cleavage 24 The hypoblast 288 The mid-blastula transition: Preparing for The primitive streak 288 gastrulation 244 Molecular mechanisms of migration through the Amphibian Gastrulation 244 primitive streak 292 Vegetal rotation and the invagination of the bottle egression of the primitive streak and epiboly of the cells 245 ectoderm 293 I S/DEU/GHTS SPECULATIONS Fibronectin and the Axis Specification and the Avian "Organizer"295 Pathways for Mesodermal Migration 250 The role of gravity and the PMZ 295 Epiboly of the prospective ectoderm 251 The chick "organizer"296 Progressive Determination of the Amphibian Anterior-posterior patterning 297 Axes 252 Left-right axis formation 298 Hans Spemann: Inductive interactions in regulative EARLY MAMMALIAN DEVELOPMENT 300 ent 2 Cleavage 300 Hans Spemann and Hilde Mangold: Primary embrvonic induction 255 The unique nature of mammalian cleavage 300 Molecular Mechanisms of Amphibian Axis Compaction 301 Formation 256 a S/DEL/GHTS SPECULATIONS Trophoblast or ICM? 302 How does the organizer form? 257 Escape from the zona pellucida 304 Functions of the organ Mammalian Gastrulation 304 Induction of neural ectoderm and dorsal Modifications for development inside another BMP inhibitors 263 organism 305 cers: The BMPs 265 Formation of the extraembryonic membranes 307 N SIDELIGHTS SPECULATIONS Twins and Chimeras 309
CONTENTS The anterior organizing center: The Bicoid and Hunchback gradients 223 The terminal gene group 225 Summarizing early anterior-posterior axis specification in Drosophila 226 Segmentation Genes 226 • SIDELIGHTS & SPECULATIONS Segments and Parasegments 227 The gap genes 228 The pair-rule genes 229 The segment polarity genes 231 The Homeotic Selector Genes 234 Initiating and maintaining the patterns of homeotic gene expression 235 Realisator genes 236 Axes and Organ Primordia: The Cartesian Coordinate Model 236 Coda 237 CHAPTER 7 Amphibians and Fish: Early Development and Axis Formation 241 EARLY AMPHIBIAN DEVELOPMENT 242 Fertilization, Cortical Rotation, and Cleavage 242 Unequal radial holoblastic cleavage 243 The mid-blastula transition: Preparing for gastrulation 244 Amphibian Gastrulation 244 Vegetal rotation and the invagination of the bottle cells 245 • SIDELIGHTS & SPECULATIONS Fibronectin and the : '-'r '.a\s for Mesodermal Migration 250 Epiboly of the prospective ectoderm 251 Progressive Determination of the Amphibian Axes 252 -:~f fre~2r-.: Inductive interactions in regulative development 253 Hans Spemann and Hilde Mangold: Primary embryonic induction 255 Molecular Vlechanisms of Amphibian Axis Formation 256 How does the organizer form? 257 Functions of the organizer 262 Induction of neural ectoderm and dorsal mesoderm: BMP inhibitors 263 Epidermal inducers: The BMPs 265 • SIDELIGHTS & SPECULATIONS BMP4 and Geoffrey's Lobster 267 The Regional Specificity of Neural Induction 267 The head inducer: Wnt inhibitors 268 Trunk patterning: Wnt signals and retinoic acid 270 Specifying the Left-Right Axis 272 EARLYZEBRAFISH DEVELOPMENT 273 Cleavage 275 Gastrulation and Formation of the Germ Layers 277 Axis Formation in Zebrafish 278 Dorsal-ventral axis formation 278 The fish Nieuwkoop center 281 Anterior-posterior axis formation 282 Left-right axis formation 282 Coda 283 CHAPTER 8 Birds and Mammals: Early Development and Axis Formation 287 EARLY DEVELOPMENT IN BIRDS 287 Cleavage 287 Gastrulation of the Avian Embryo 288 The hypoblast 288 The primitive streak 288 Molecular mechanisms of migration through the primitive streak 292 Regression of the primitive streak and epiboly of the ectoderm 293 Axis Specification and the Avian "Organizer" 295 The role of gravity and the PMZ 295 The chick "organizer" 296 Anterior-posterior patterning 297 Left-right axis formation 298 EARLY MAMMALIAN DEVELOPMENT 300 Cleavage 300 The unique nature of mammalian cleavage 300 Compaction 301 • SIDELIGHTS & SPECULATIONS Trophoblast or ICM? 302 Escape from the zona pellucida 304 Mammalian Gastrulation 304 Modifications for development inside another organism 305 Formation of the extraembryonic membranes 307 • SIDELIGHTS & SPECULATIONS Twins and Chimeras 309
Mammalian Axis Formation 311 Experimental analysis of the Hox code 315 The anterior-posterior axis: Two signaling The Dorsal-Ventral and Left-Right Axes 316 centers 311 The dorsal-ventral axis 316 Anterior-posterior patterning by FGF and retinoic acid gradients 312 Coda 319 Anterior-posterior patterning: The Hox code hypothesis 314 PART THE STEM CELL CONCEPT Introducing Organogenesis 323 The Stem Cell Concept 323 Mesenchymal Stem Cells: Multipotent Stem Cell Vocabulary 326 Adult Stem Cells 330 Adult stem Cells 327 A New Perspective on Organogenesis 331 Adult Stem Cell Niches 328 chAPTER 9 Cell Differentiation in the vertebrate Eye 362 The Emergence of the ectoderm Neural retina differentiation 362 Lens and cornea differentiation 364 Central Nervous System and Epidermis 333 THE EPIDERMIS AND ITS CUTANEOUS APPENDAGES 365 Establishing the Neural Cells 333 CONSTRUCTING THE CENTRAL NERVOUS Origin of the Epidermis 365 SYSTEM 334 The Cutaneous Appendages 366 Formation of the neural tube 334 I SIDELIGHTS SPECULATIONS EDAR Syndromes 369 Primary neurulation 335 Secondary neurulation CHAPTER 10 BUILDING THE BRAIN Neural Crest Cells and axonal Differentiation of the Neural Tube 341 The anterior-posterior axis 341 Specificity 373 The dorsal-ventral axis 343 THE NEURAL CREST 373 Differentiation of Neurons in the Brain 345 Specification of Neural Crest Cells 374 Tissue Architecture of the Central Nervous System 34 Regionalization of the Neural Crest 376 Spinal cord and medulla organization 349 Trunk Neural Crest 3 Cerebellar organization 350 Migration pathways of trunk neural crest cells 377 Cerebral organization 351 The mechanisms of trunk neural crest migration 378 H SIDELIGHTS SPECULATIONS Adult Neural Stem The ventral pathway 379 Cells 354 The dorsolateral migration pathway 382 I SIDELIGHTS SPECULATIONS The Unique Development Cranial Neural Crest 383 of the human brain 356 Intramembranous ossification: Neural crest-derive DEVELOPMENT OF THE VERTEBRATE EYE 359 head skeleton 385 The Dynamics of Optic Development 359 Coordination of face and brain growth 387 Formation of the Eye Field 359 Tooth formation 388 Cardiac Neural Crest 388
V_1^IN I CiN I O Mammalian Axis Formation 311 The anterior-posterior axis: Two signaling centers 311 Anterior-posterior patterning by FGF and retinoic acid gradients 312 Anterior-posterior patterning: The Hox code hypothesis 314 Experimental analysis of the Hox code 315 The Dorsal-Ventral and Left-Right Axes 316 The dorsal-ventral axis 316 The left-right axis 317 Coda 319 PART THE STEM CELL CONCEPT Introducin Organogenesis 323 The Stem Cell Concept 323 Stem Cell Vocabulary 326 Adult Stem Cells 327 Adult Stem Cell Niches 328 Mesenchymal Stem Cells: Multipotent Adult Stem Cells 330 A New Perspective on Organogenesis 331 CHAPTER 9 The Emergence of the Ectoderm: Central Nervous System and Epidermis 333 Establishing the Neural Cells 333 CONSTRUCTING THE CENTRAL NERVOUS SYSTEM 334 Formation of the Neural Tube 334 Primary neurulation 335 Secondary neurulation 340 BUILDING THE BRAIN 341 Differentiation of the Neural Tube 341 The anterior-posterior axis 341 The dorsal-ventral axis 343 Differentiation of Neurons in the Brain 345 Tissue Architecture of the Central Nervous System 348 Spinal cord and medulla organization 349 Cerebellar organization 350 Cerebral organization 351 • SIDELIGHTS & SPECULATIONS Adult Neural Stem Cells 354 • SIDELIGHTS & SPECULATIONS The Unique Development of the Human Brain 356 DEVELOPMENT OF THE VERTEBRATE EYE 359 The Dynamics of Optic Development 359 Formation of the Eye Field 359 Cell Differentiation in the Vertebrate Eye 362 Neural retina differentiation 362 Lens and cornea differentiation 364 THE EPIDERMIS AND ITS CUTANEOUS APPENDAGES 365 Origin of the Epidermis 365 The Cutaneous Appendages 366 • SIDELIGHTS & SPECULATIONS EDAR Syndromes 369 CHAPTER 10 Neural Crest Cells andAxonal Specificity 373 THE NEURAL CREST 373 Specification of Neural Crest Cells 374 Regionalization of the Neural Crest 376 Trunk Neural Crest 377 Migration pathways of trunk neural crest cells 377 The mechanisms of trunk neural crest migration 378 The ventral pathway 379 The dorsolateral migration pathway 382 Cranial Neural Crest 383 Intramembranous ossification: Neural crest-derived head skeleton 385 Coordination of face and brain growth 387 Tooth formation 388 Cardiac Neural Crest 388
CONTENTS Cranial Placodes 389 Vertebrae formation 431 U SIDELIGHTS SPECULATIONS Cranial Neural Crest C Dorsal Aorta Formation 432 Migration and Specification 391 Tendon Formation: The Syndetome 432 NEURONAL SPECIFICATION AND AXONAL INTERMEDIATE MESODERM: THE UROGENITAL SPECIFICITY 392 SYSTEM 434 The Generation of Neuronal Diversity 393 The Progression of Kidney Types 434 Pattern Generation in the Nervous System 394 Specification of the Intermediate Mesoderm Cell adhesion and contact guidance by attraction Pax2/8 and Lim1 435 and repulsion 396 Guidance by diffusible molecules 398 Reciprocal Interactions of Developing Kidney Tissues 436 Target selection 399 Mechanisms of reciprocal induction 437 Forming the synapse: Activity-dependent Coda 442 development 402 Differential survival after innervation: Neurotrophic factors 403 CHAPTER 12 H SIDELIGHTS SPECULaTIoNs The Brainbow 404 Paths to glory: The travels of the retinal ganglion Lateral Plate Mesoderm and the axons 404 Endoderm 445 The Development of Behaviors: Constancy and Plasticity 408 LATERAL PLATE MESODERM 445 Heart Development 446 CHAPTER 11 Specification of heart tissue 446 Migration of cardiac precursor cells 448 Paraxial and intermediate Determination of anterior and posterior cardiac Mesoderm 413 domains 450 Heart cell differentiation 450 PARAXIAL MESODERM: THE SOMITES AND Fusion of the heart rudiments and initial heartbeats THEIR DERIVATIVES 414 Formation of the Somites 415 Looping and formation of heart chambers 453 Periodicity of somite formation 417 I S/DELIGHTS SPECULATIONS Redirecting Blood Flow in the Newborn Mammal 455 Where somites form: The Notch pathway 417 I SIDELIGHTS SPECULATIONS Coordinating Waves and Formation of Blood Vessels 456 Clocks in Somite Formation 419 Constraints on the construction of blood vessels 456 Separation of somites from the unsegmented Vasculogenesis: The initial formation of blood mesoderm 420 ls458 Epithelialization of the somites 420 Angiogenesis: Sprouting of blood vessels and Somite specification along the anterior-posterior remodeling of vascular axis 420 Arterial and venous differentiation 462 Differentiation of the somites 421 Determination of the sclerotome 424 Anti-angiogenesis in normal and abnormal Determination of the central dermamyotome 425 Determination of the myotome 425 The lymphatic vessels 465 Myogenesis: The Generation of Muscle 426 Hematopoiesis: The Stem Cell Concept 466 Myogenic bHLH proteins 426 Sites of hematopoiesis 466 Specification of muscle progenitor cells 426 Committed stem cells and their fates 468 Hematopoietic inductive microenvironments 47( Osteogenesis: The Development of Bones 428 Stem cell niche construction 470 Endochondral ossification 428
xii CONTENTS Cranial Placodes 389 • SIDELIGHTS & SPECULATIONS Cranial Neural Crest Cell Migration and Specification 391 NEURONAL SPECIFICATION AND AXONAL SPECIFICITY 392 The Generation of Neuronal Diversity 393 Pattern Generation in the Nervous System 394 Cell adhesion and contact guidance by attraction and repulsion 396 Guidance by diffusible molecules 398 Target selection 399 Forming the synapse: Activity-dependent development 402 Differential survival after innervation: Neurotrophic factors 403 • SIDELIGHTS & SPECULATIONS The Brainbow 404 Paths to glory: The travels of the retinal ganglion axons 404 The Development of Behaviors: Constancy and Plasticity 408 CHAPTER 11 Paraxial and Intermediate Mesoderm 413 PARAXIAL MESODERM: THE SOMITES AND THEIR DERIVATIVES 414 Formation of the Somites 415 Periodicity of somite formation 417 Where somites form: The Notch pathway 417 • SIDELIGHTS & SPECULATIONS Coordinating Waves and Clocks in Somite Formation 419 Separation of somites from the unsegmented mesoderm 420 Epithelialization of the somites 420 Somite specification along the anterior-posterior axis 420 Differentiation of the somites 421 Determination of the sclerotome 424 Determination of the central dermamyotome 425 Determination of the myotome 425 Myogenesis: The Generation of Muscle 426 Myogenic bHLH proteins 426 Specification of muscle progenitor cells 426 Myoblast fusion 427 Osteogenesis: The Development of Bones 428 Endochondral ossification 428 Vertebrae formation 431 Dorsal Aorta Formation 432 Tendon Formation: The Syndetome 432 INTERMEDIATE MESODERM: THE UROGENITAL SYSTEM 434 The Progression of Kidney Types 434 Specification of the Intermediate Mesoderm: Pax2/8 and Lim1 435 Reciprocal Interactions of Developing Kidney Tissues 436 Mechanisms of reciprocal induction 437 Coda 442 CHAPTER 12 Lateral Plate Mesoderm and the Endoderm 445 LATERAL PLATE MESODERM 445 Heart Development 446 Specification of heart tissue 446 Migration of cardiac precursor cells 448 Determination of anterior and posterior cardiac domains 450 Heart cell differentiation 450 Fusion of the heart rudiments and initial heartbeats 452 Looping and formation of heart chambers 453 • SIDELIGHTS & SPECULATIONS Redirecting Blood Flow in the Newborn Mammal 455 Formation of Bloodvessels 456 Constraints on the construction of blood vessels 456 Vasculogenesis: The initial formation of blood vessels 458 Angiogenesis: Sprouting of blood vessels and remodeling of vascular beds 461 Arterial and venous differentiation 462 Organ-specific capillary formation 463 Anti-angiogenesis in normal and abnormal development 465 The lymphatic vessels 465 Hematopoiesis: The Stem Cell Concept 466 Sites of hematopoiesis 466 Committed stem cells and their fates 468 Hematopoietic inductive microenvironments 470 Stem cell niche construction 470
ENDODERM 471 Growth hormone and estrogen receptors 509 The Pharynx 47 Parathyroid hormone-related peptide and Indian The Digestive Tube and Its Derivatives 473 Specification of the gut tissue 473 Coda 509 Liver, pancreas, and gallbladder 475 SIDELIGHTS SPECULATIONS Specification of Liver and CHAPTER 14 Pancreas 476 he Respiratory Tube 478 Sex Determination 511 he Extraembryonic Membranes 480 CHROMOSOMAL SEX DETERMINATION 512 The amnion and chorion 481 The Mammalian Pattern: Primary and Secondary The allantois and yolk sac 482 Sex Determination 512 Primary Sex Determination in Mammals 513 CHAPTER 13 ng Development of the Tetrapod Mechanisms of mammalian primary sex ing decisions 515 Limb 485 The ovary pathway: Wnt4 and R-spondin1 517 The testis pathway 518 Formation of the limb bud 486 The right time and the right place 521 Specification of the limb fields 486 I SIDELIGHTS SPECULATIONS Mysteries of Gonad Induction of the early limb bud: Wnt proteins and Differentiation 521 fibroblast growth factors 488 Secondary Sex Determination in Mammals Specification of forelimb or hindlimb 488 Hormonal Regulation of the Sexual Generating the Proximal-Distal Axis of the Phenotype 523 Limb 491 The genetic analysis of secondary sex The apical ectodermal ridge 491 determination 523 FGFs in the induction of the aer 492 Brain sex: Secondary sex determination through Specifying the limb mesoderm: Determining the another pathway? 525 proximal-distal polarity of the limb 493 n SIDELIGHTS SPECULaTioNs Brain Sex: Sex A reaction-diffusion model for limb specification Determinants and Behaviors in mice and rats 526 Chromosomal Sex Determination in Specification of the Anterior-Posterior Axis 495 Drosophila 529 The zone of polarizing activity 495 The Sex-lethal gene 529 I SIDELIGHTS SPECULATIONS Hox Gene Changes during Doublesex: The switch gene for sex Limb Development 498 specifying digit identity by Sonic hedgehog 50 Brain sex in Drosophila 53 Generation of the Dorsal- Ventral Axis 502 Dosage Compensation 534 Coordinating the Three Axes 502 ENVIRONMENTAL SEX DETERMINATION 534 Cell Death and the formation of Digits and Temperature-Dependent Sex Determination in Joints 504 Reptiles 534 Sculpting the autopod 504 The aromatase hypothesis for environmental sex determination 535 I SIDELIGHTS SPECULATIONS Limb Development and Evolution 505 Estrogens, aromatase, sex reversal, and conservation Forming the joints 507 Location-Dependent Sex Determination 536 Continued Limb Growth: Epiphyseal Plates 508 Coda 538 Fibroblast growth factor receptors: Dwarfism 508
LUNItNI!> XIII ENDODERM 471 The Pharynx 471 The Digestive Tube and Its Derivatives 473 Specification of the gut tissue 473 Liver, pancreas, and gallbladder 475 • SIDELIGHTS & SPECULATIONS Specification of Liver and Pancreas 476 The Respiratory Tube 478 The Extraembryonic Membranes 480 The amnion and chorion 481 The allantois and yolk sac 482 CHAPTER 13 Development of the Tetrapod Limb 485 Formation of the Limb Bud 486 Specification of the limb fields 486 Induction of the early limb bud: Wnt proteins and fibroblast growth factors 488 Specification of forelimb or hindlimb 488 Generating the Proximal-Distal Axis of the Limb 491 The apical ectodermal ridge 491 FGFs in the induction of the AER 492 Specifying the limb mesoderm: Determining the proximal-distal polarity of the limb 493 A reaction-diffusion model for limb specification 494 Specification of the Anterior-Posterior Axis 495 The zone of polarizing activity 495 • SIDELIGHTS & SPECULATIONS Hox Gene Changes during Limb Development 498 Specifying digit identity by Sonic hedgehog 500 Generation of the Dorsal-Ventral Axis 502 Coordinating the Three Axes 502 Cell Death and the Formation of Digits and Joints 504 Sculpting the autopod 504 • SIDELIGHTS & SPECULATIONS Limb Development and Evolution 505 Forming the joints 507 Continued Limb Growth: Epiphyseal Plates 508 Fibroblast growth factor receptors: Dwarfism 508 Growth hormone and estrogen receptors 509 Parathyroid hormone-related peptide and Indian hedgehog 509 Coda 509 CHAPTER 14 Sex Determination 511 CHROMOSOMAL SEX DETERMINATION 512 The Mammalian Pattern: Primary and Secondary Sex Determination 512 Primary Sex Determination in Mammals 513 The developing gonads 513 Mechanisms of mammalian primary sex determination: Making decisions 515 The ovary pathway: Wnt4 and R-spondinl 517 The testis pathway 518 The right time and the right place 521 • SIDELIGHTS & SPECULATIONS Mysteries of Gonad Differentiation 521 Secondary Sex Determination in Mammals: Hormonal Regulation of the Sexual Phenotype 523 The genetic analysis of secondary sex determination 523 Brain sex: Secondary sex determination through another pathway? 525 • SIDELIGHTS & SPECULATIONS Brain Sex: Sex Determinants and Behaviors in Mice and Rats 526 Chromosomal Sex Determination in Drosophila 529 The Sex-lethal gene 529 Doublesex: The switch gene for sex determination 532 Brain sex in Drosophila 533 Dosage Compensation 534 ENVIRONMENTAL SEX DETERMINATION 534 Temperature-Dependent Sex Determination in Reptiles 534 The aromatase hypothesis for environmental sex determination 535 Estrogens, aromatase, sex reversal, and conservation biology 535 Location-Dependent Sex Determination 536 Coda 538