I have been interested in and studying skeletal tissues since my undergraduate days in Australia in the 1960s. Those early studies on the development of secondary cartilage in embryonic birds, first published in 1967, have come full circle with the discovery of secondary cartilage in dinosaurs12. Bird watching really is flying reptile watching. Skeletal tissue development and evolution, the embryonic origins of skeletal tissues (especially those that arise from neural crest cells), and integrating development and evolution in what is now known as evo-devo have been my primary preoccupations over the past 50+ years.
Bones and Cartilage provides the most in-depth review and synthesis assembled on the topic, across all vertebrates. It examines the function, development and evolution of bone and cartilage as tissues, organs and skeletal systems. It describes how bone and cartilage develop in embryos and are maintained in adults, how bone is repaired when we break a leg, or regenerates when a newt grows a new limb, or a lizard a new tail. The second edition of Bones and Cartilage includes the most recent knowledge of molecular, cellular, developmental and evolutionary processes, which are integrated to outline a unified discipline of developmental and evolutionary skeletal biology. Additionally, coverage includes how the molecular and cellular aspects of bones and cartilage differ in different skeletal systems and across species, along with the latest studies and hypotheses of relationships between skeletal cells and the most recent information on coupling between osteocytes and osteoclasts All chapters have been revised and updated to include the latest research. - Offers complete coverage of every aspect of bone and cartilage, with updated references and extensive illustrations- Integrates development and evolution of the skeleton, as well a synthesis of differentiation, growth and patterning- Treats all levels from molecular to clinical, embryos to evolution, and covers all vertebrates as well as invertebrate cartilages- Includes new chapters on evolutionary skeletal biology that highlight normal variation and variability, and variation outside the norm (neomorphs, atavisms)- Updates hypotheses on the origination of cartilage using new phylogenetic, cellular and genetic data- Covers stem cells in embryos and adults, including mesenchymal stem cells and their use in genetic engineering of cartilage, and the concept of the stem cell niche
Front Cover 1
Bones and Cartilage 4
Copyright Page 5
Contents 6
Preface 16
Organisational Changes 17
Conceptual Changes 17
Epigraphs 18
I. Vertebrate Skeletal Tissues 20
1 Vertebrate Skeletal Tissues 22
Bone 24
Cartilage 24
Dentine 30
Enamel 30
Intermediate Tissues 32
Cementum 33
Enameloid 33
Chondroid and Chondroid Bone 33
Cartilage into Bone: Direct and Indirect Ossification 34
Notes 35
2 Bone 36
Discovery of the Basic Structure of Bone 36
Cellular Bone 38
Osteocytes 40
Sclerostin 40
Osteocyte Connections, Function and Maintenance 41
Intramembranous and Endochondral Bone 42
Embryonic Origins 42
Subperiosteal Ossification and Suppression of the Cartilage Phase 42
Metabolic Differences Between Bone Types 43
Morphogenetic Differences Between Bones 44
Osteones 45
Growth 47
Regional Remodelling 48
Ageing 48
Ageing at the Cellular Level 48
Ageing at Cellular and Tissue Levels 49
Ageing at the Organ Level 49
Ageing of the Skeletal System 49
Osteones Over Time 49
Acellular Bone 50
Caisson Disease and Abnormal Acellular Bone in Mammals 50
Acellular Bone in Teleost Fishes 51
Development 51
Mechanical Properties 52
Resorption 53
Repair of Fractures 54
Ca2+ Regulation 55
Aspidine 58
Bone in Sharks and Rays (Cartilaginous Fishes) 58
Notes 59
3 Vertebrate Cartilages 62
Types 62
Chondrones 62
Cartilage Growth 65
Cartilage Canals 66
Secondary Centres of Ossification 67
Elastic Cartilage 68
Elastic Fibres 68
The Cells 68
Elastic Cartilage, Adipocytes and Intermediate Tissues 70
Shark Cartilage 71
Development and Mineralisation 71
Tesserae 72
Growth 73
Inhibition of Vascular Invasion 73
Lampreys 73
Mucocartilage 74
Lamprin 75
Mineralisation 76
Hagfish 76
Acellular Cartilage in a Freshwater Stingray 77
Notes 77
II. Origins and Types of Skeletal Tissues 80
4 Invertebrate Cartilages, Notochordal Cartilage and Cartilage Origins 82
Chondroid and Cartilage 82
Odontophore Cartilage in Caenogastropods 83
Branchial (Gill Book) Cartilage in the Horseshoe Crab, Limulus polyphemus 84
Cranial Cartilages in Squid, Cuttlefish and Octopuses 84
Composition of the Extracellular Matrix 85
Glycosaminoglycans 85
Collagens 85
Tentacular Cartilage in Polychaete Annelids 88
Lophophore Cartilage in an Articulate Brachiopod, Terebratalia transversa 88
Mineralisation of Invertebrate Cartilages 88
Cartilage Origins 93
Hemichordates 93
Notochordal Cartilage 95
Notes 96
5 Intermediate Tissues 98
Scleroblasts 98
Modulation and Intermediate Tissues 99
Cartilage from Fibrous Tissue and Metaplasia 101
Metaplasia of Epithelial Cells to Chondroblasts or Osteoblasts 102
Chondroid 103
Chondroid in Teleosts 103
Chondroid in Mammals 105
Chondroid Bone 106
Chondroid Bone in Teleosts 106
Trematode Infections and Biomechanical Stress 106
Kype Tissues in Migrating Atlantic Salmon, Salmo salar 107
Chondroid Bone and Pharyngeal Jaws 109
Chondroid Bone in Mammals 110
Tissues Intermediate Between Bone and Dentine 111
Dentine 111
Cementum 113
Enameloid: a Tissue Intermediate Between Dentine and Enamel 114
Notes 115
6 Lessons from Fossils 118
Fossilised Skeletal Tissues 118
All Four Skeletal Tissues Are Ancient 118
A Family of Skeletal Tissues in Fossil Agnatha 121
Dinosaur Bone, Dinosaur Growth and Life History 122
Patterns of Ossification and Bone Growth 123
Developing Skeletons in Fossils 124
Patterns of Growth and Homoeostasis 124
Palaeopathology 125
Conodonts 125
What Are Conodonts? 126
Conodont Elements as Teeth and Conodonts as Chordates 127
Conodonts as Chordates 127
Conodont Elements as Teeth 127
Notes 128
III. Unusual Modes of Skeletogenesis 130
7 Horns and Ossicones 132
Horns 132
Distribution of Horns as Organs 133
Bovidae 133
Rhinos 134
Titanotheres 137
Pronghorn Antelopes 137
Giraffes 137
Horn as a Tissue 139
Development and Growth of Horns 140
Notes 141
8 Antlers 142
Antlers 142
Combat and Dominance 142
Size and Absence of Antlers 142
Initiation of Antler Formation 143
Pedicle Formation 143
The Antler Bud and Dermal–Epidermal Interactions 145
Hormonal Control of Pedicle Development and Growth 146
Antler Replacement 146
The Shedding Cycle 146
Histogenesis of Antlers 148
White-Tailed Deer, American Elk, European Fallow and Roe Deer 148
Rocky Mountain Mule Deer 150
Sika Deer 150
Hormones, Photoperiod and Antler Growth 150
Photoperiod and Testosterone 152
Parathyroid Hormone and Calcitonin 153
Notes 153
9 Tendon Skeletogenesis and Sesamoids 156
Tendons and Skeletogenesis 156
Difficult Cases 157
Fibrocartilage in Tendons 157
Rodent Achilles Tendons 158
Ossification of Avian Tendons 160
Formation and Composition of Tendon Fibrocartilages 160
Condensation 160
Scleraxis 161
Composition of Tendon Extracellular Matrices 162
Sesamoids 163
Anuran Amphibians 164
Reptiles 165
Birds 165
Notes 167
IV. Stem and Progenitor Cells 170
10 Embryonic Stem and Progenitor Cells 172
Stem Cells 172
Set-Aside Cells 174
Periosteal Progenitor Cell for Periosteal Osteogenesis in Long Bones 176
Modulation of Synthetic Activity and Differentiative Pathways of Cell Populations 179
Fibroblast–Chondroblast Modulation 179
Modulation of Glycosaminoglycan Synthesis 179
Modulation of Synthetic Activity and Differentiative Pathways in Single Cells 180
Degradative Activity 180
Notes 183
11 Stem and Progenitor Cells in Adults 186
Fibroblast Colony-Forming Cells 186
Niches and Haemospheres 188
Osteogenic Precursor Cells 188
Clonal Analysis 189
Lineages of Cells 189
Dexamethasone, Osteogenesis and Chondrogenesis 189
Epithelial Induction of Ectopic Bone 191
Transitional Epithelium of the Urinary Bladder 191
Epithelial Cell Lines 192
Chondrogenic Precursor Cells 194
Conversion to Stem Cells 194
Mesenchymal Stem Cells 195
miRNAs 195
Neural Crest–Derived Stem Cells 196
Notes 196
V. Skeletogenic Cells 198
12 Bipotential Osteochondroprogenitor Cells 200
Identifying Osteochondroprogenitor Cells 200
Execrable Terminology 201
Features 201
Cell Cycle Dynamics 201
Bipotential Progenitor Cells for Osteogenesis and Chondrogenesis 202
Bipotential Cell Populations or Bipotential Cells? 202
Uncovering Bipotentiality 202
Discovering Bipotentiality 203
Biochemical and Metabolic Markers 203
Collagen Types 204
The Tumour Suppressor Gene p53 205
Condylar Cartilage on the Condylar Process of the Mammalian Dentary 208
Histodifferentiation and Scurvy 208
One or Two Cell Populations 209
Two Cell Populations 209
One Cell Population 209
Evidence Against Bipotentiality 209
Evidence Supporting Bipotentiality 210
Homogeneous or Heterogeneous Cell Population? 212
Secondary Cartilage on Avian Membrane Bones 213
Notes 217
13 Dedifferentiation of Chondrocytes and Endochondral Ossification 218
The Fate of Hypertrophic Chondrocytes of the Condylar Cartilage 218
The Temporomandibular Joint 218
Hypertrophic Chondrocytes Survive 219
Hypertrophic Chondrocytes Transform to Osteoprogenitor Cells 219
Meckel’s Cartilage 221
Fate of Meckel’s Cartilage in Mammals 221
Middle Ear Ossicles 224
The Poster Child for Evolution 224
Fossil Evidence 225
Embryological Evidence 227
Homeobox Gene Control of Mandibular Skeletal Development 228
Msx and Dlx genes 228
Msx Genes and Bmp4 228
Prx1, Prx2 228
Alx3 231
Pitx1 231
Dedifferentiation During Endochondral Bone Formation 232
Rodent Ribs 232
Mice 232
Rats 233
Appendicular Long Bones 234
Enzyme Activity 234
Evidence from 3H-Thymidine Labelling and Other Approaches 235
Murine Interpubic Joints 235
Notes 237
14 Dedifferentiation and Stem Cells: Regeneration of Urodele Limbs and Mammalian Fingertips 238
Urodele Limb Regeneration 238
Dedifferentiation 239
Morphological Dedifferentiation 239
Functional Dedifferentiation 239
Hyaluronan 239
Blastema Formation 240
More Than One Cell Fate 241
Myoblast and Chondroblast Fates 241
Innervation 242
Aneurogenic Limbs 243
Electrical Signals? 245
Hox Genes 245
FgfR1 and FgfR2 246
Radical Fringe 246
Why Frogs Cannot Regenerate Their Limbs 246
Anuran and Urodele Regeneration 247
Augmenting Regeneration 250
Fingertips of Mice, Monkeys and Humans 250
Monkeys and Humans 250
Mice 251
Mouse Digit and Newt Limb Regeneration 252
Demineralised Bone Matrix and Skeletal Repair 252
The Approach 252
Cartilage Induction but Bone Formation 253
The Active Agent: Bmp 254
Carriers 255
Notes 255
15 Cells to Make and Cells to Break 258
Clasts and Blasts 258
Resorption of Bone 258
Proximity to Bone Matrix 259
Vacuolar Proton Pump (V-ATPase) 259
Worms that Digest Whale Bones 259
Osteoclasts In Vitro 259
Coupling Bone Resorption to Bone Formation 260
Coupling Osteoblasts and Osteoclasts 260
Parathyroid Hormone (PTH) 260
TGFß Signalling 261
Osteoprotegerin and RankL 261
Osteocalcin and Mechanical Stimulation 261
When Coupling Goes Awry 263
Osteoporosis 264
Statins 265
Trap-Staining for Osteoclasts 265
Mammalian Osteoclasts 265
Teleost Osteoclasts 265
Nitric Oxide: It’s a Gas 266
Progenitor Cells for Osteoblasts and Osteoclasts 266
Japanese Quail: Domestic Fowl Chimeras 267
Osteopetrosis and Osteoclast Origins 269
IS The Lineage Macrophage & #8594
Phagocyte–Macrophage Origin 271
Interleukins 272
Evidence Against Monocytes 274
Evidence for Monocytes 274
Chondroclasts and Osteoclasts 274
Synovial Cells and Reportion of Articular Cartilage 275
Notes 275
VI. Embryonic Origins 278
16 Skeletal Origins: Somitic Mesoderm, Vertebrae, Pectoral and Pelvic Girdles 280
Somitic Mesoderm and the Origin of the Vertebral Column 281
Paraxial Mesoderm& #8594
Sclerotome Formation, Migration and Vertebral Development 281
Origin of Teleost Vertebrae in the Notochordal Sheath 285
Resegmentation of Somites 287
Intervertebral Discs and Nucleus Pulposus 287
Somites Provide the Muscles for Limb Buds 288
Pectoral and Pelvic Girdles 290
Pectoral Girdle 290
Scapula Development (and Evolution) 290
The Blade of the Scapula 291
Pelvic Girdle 292
The Clavicle: Even More Surprising 292
Clavicular Development in Humans 293
Other Mammals 293
Mammals That Lack Clavicles 294
Avian Clavicles 294
Wishbone or Clavicles in Birds and Dinosaurs 295
The Interclavicle 296
Notes 297
17 Skeletal Origins: Neural Crest Cells 300
Different Mesenchymes, Same Tissues 300
Neural Crest as a Source of Skeletal Cells 301
Evidence of Skeletogenic Potential 301
Ablation and Transplantation of Urodele Neural Crest 302
3H-Thymidine-Labelling of Neural Crest Cells in Chicken Embryos 304
Quail–Chick Chimeras and the Avian Neural Crest 305
DiI-Labelling and Lungfish Neural Crest 310
Transgenic Labelling of Zebrafish Embryos 311
Transgenic Labelling of Mouse Embryos 311
Neural Crest–Mesoderm Boundaries 312
Mutants and the Neural Crest 313
Regionalisation of the Cranial Neural Crest 313
Cranial and Trunk and Neural Crest 314
Turtle Shells 314
Chondrogenesis from Trunk Neural Crest Cells 314
From Skeletal Origins to Skeletal Initiation 316
Notes 316
18 Epithelial–Mesenchymal Interactions Initiate Skeletogenesis 318
Urodele Amphibians: Chondrogenesis 320
Avian Mandibles: Chondrogenesis and Osteogenesis 320
Meckel’s Cartilage 321
Molecular Mechanisms 321
Fgfs 322
Hoxa Genes 322
Mandibular Bones 322
Maxillary Bones 325
Ruling Out a Role for Meckel’s Cartilage in Mandibular Bone Formation 325
Mammalian Mandibular Skeleton 326
Molecular Mechanisms 326
Endothelin1 (Edn1) 326
The Dlx and Msx Gene Families and Murine Craniofacial Development 327
Dlx Genes in Shark, Skate and Paddlefish Craniofacial Development 330
Teleost Mandibular Arch Skeleton 330
Dlx Genes 331
Fgfs 331
Hoxd4 and Retinoic Acid 331
Mutants 332
Lateral Line, Neuromasts and Dermal Bone 332
Hope from a Single Trout 332
Notes 334
VII. Getting Started 336
19 The Membranous Skeleton: Condensations 338
The Membranous Skeleton 339
Characterising and Visualising Condensations 341
How Condensations Arise 344
Altered Mitotic Activity 344
Changing Cell Density 344
Aggregation and/or Failure to Disperse 345
Molecular Control 346
NCam 346
Cadherins and NCam 347
cAMP and p-35 347
Pax, Prx and Alx 348
Establishing Boundaries of condensations 348
Syndecan and Tenascin 348
Fgfs 349
Wnt7a 349
Notes 349
20 From Condensation to Differentiation 352
Condensation Growth 352
Lessons from Mutants 353
Talpid3 Chickens 353
Brachypod (bpH) Mouse Mutant 354
Adhere, Proliferate and Grow 355
Gap Junctions 355
Limb-bud Mesenchyme 355
Craniofacial Mesenchyme 355
Additional Molecular Signals and Condensation 355
Forkhead Transcription Factors 355
Smad4 356
Sox9 358
Hoxa2 and Hoxa13 358
Condensation Position and Shape 358
Establishing Condensation Size 359
Bmps 359
Fibronectin 359
Chick Fore- and Hind Limb Buds 360
Hyaluronan 360
Persistence of Condensations 361
Hoxa2 and Incipient Condensations 361
From Condensation to Overt Differentiation 363
Bmps 363
Tenascin and NCam 363
Runx2 364
‘Chondrogenic’ Genes and Early Intramembranous Ossification? 366
Notes 367
21 Skulls, Eyes and Ears: Condensations and Tissue Interactions 368
The Skull 368
Avian Skull Development 369
Mammalian Skull Development 370
The Cartilaginous Skull 372
Type II Collagen 372
Otic, Optic and Nasal Capsules 372
The Otic Vesicle 373
Tympanic Cartilages 374
Scleral Cartilage 375
Chondrogenic Mesenchyme 375
Pigmented Retinal Epithelium 376
Morphogenesis of Scleral Cartilage 376
Scleral Ossicles 377
Teleosts 378
Ossicles in Domestic Chickens Gallus domesticus 378
Number of Ossicles 378
Epithelial Scleral Papillae 379
Focal Epithelial–Mesenchymal Interactions 380
Scaleless Mutant Fowl 381
A Role for Tenascin? 381
Bmp and Hedgehog Signalling 384
Notes 384
VIII. Similarity and Diversity 386
22 Chondrocyte Diversity 388
Chondrocytes Segregate from Precursors 388
Formation of Perichondria 390
Morphogenetic Specificity of Cartilages 390
Cartilages of Different Embryological Origins 392
Chondrocyte Hypertrophy 393
Vascular Invasion 393
Type X Collagen 394
Regulation of the Synthesis of Type X Collagen 394
Type X Does Not Always Indicate Hypertrophy 396
Regulation of Chondrocyte Hypertrophy 396
Hormones and Chondrocyte Hypertrophy 398
Type X and Mineralisation 398
Birds 398
Frogs 398
Rickets 398
Matrix Vesicles 398
Hypertrophic Chondrocytes and Subperiosteal Ossification 400
Brachypod (bpH) Mice 401
Early Changes 401
Fibulae 402
A Role for Wnts 404
Notes 404
23 Cartilage Diversity 406
Sternal Chondrocytes 406
Synthesis of Collagen and Glycosaminoglycan 406
Differential Expression of Type II Collagen 406
Differential Synthesis and Organisation of Collagen Types 406
Type X Collagen and Hypertrophy 407
Fibronectin 407
Nanomelia 407
Tumour Invasion 409
Vascularity 409
Resisting Vascular Invasion 410
Inhibitors of Angiogenesis and Vascular Invasion 412
Vascular Endothelial Growth Factor 413
PTH–PTHrP 414
Interpubic Joints and the Transformation of Cartilage to Ligament 414
Cartilage& #8594
Mediation by Oestrogen and Relaxin 417
Modulation 418
Notes 419
24 Osteoblast and Osteocyte Diversity and Osteogenesis In Vitro 420
Bone Proteins 420
Osteocalcin 420
Osteopontin 421
Osteonectin 421
Osteocytic Osteolysis 422
Hibernation 423
Initiating Osteogenesis In Vitro from Embryonic Mesenchyme 423
Osteogenic Cells In Vitro 424
Folded Periostea and Mass Cultures 426
Prostaglandin 2 (PGE2), cAMP and Mitogen-Activated Protein Kinase (MAPK) Pathways 426
Establishing Isolated Osteoblasts and Initiating Osteogenesis In Vitro 426
Calvarial Osteoblasts In Vitro 427
Isolating Subpopulations of Calvarial Osteogenic Cells 428
Chondrogenesis from Rodent and Avian Osteogenic Cells 430
Clonal Cultures 430
Notes 431
25 Diversity of Bone as a Tissue and as an Organ 434
Heterogeneity of Response to Sodium Fluoride 434
Enhanced Cell Proliferation and Initiation of Osteogenesis 434
Interaction with Hormonal Action 436
Osteoporosis 436
Chondrogenesis 436
Mineralisation 436
Mechanical Properties of Bone 436
Alveolar Bone of Mammalian Teeth 436
Developmental Origin 436
Physiology and Circadian Rhythms 439
Penile and Clitoral Cartilages and Bones 440
Os Penis 441
Os Clitoridis 441
Hormonal Control 441
Digits and Penile Bones 442
HOXD12, HOXD13 and Polyphalangy 442
Oestrogen-Stimulated Deposition of Medullary Bone in Laying Hens 443
Oestrogen-Stimulated Resorption of Pelvic Bones in Mice 444
Notes 444
IX. Maintaining Cartilage in Good Times and in Bad 446
26 Maintaining Differentiated Chondrocytes Through Cell–Matrix Interactions 448
Differentiated Chondrocytes 448
Synthesis and Deposition of Cartilaginous ECM 448
Synthesis of CS 449
Synthesis of Type II Collagen 449
Synthesis of Collagen and CS by the Same Chondrocyte 450
Collagen Gel Culture 450
Feedback Control of the Synthesis of Glycosaminoglycans 450
Evidence from Organ Culture 450
Evidence from Chondrocyte Cell Cultures and from a Mouse Mutant 451
Interactions Between Glycosaminoglycans and Collagens Within the ECM 451
Synthesis of Collagen and CS are Regulated Independently 452
Hypertrophy 452
The Interactive ECM 453
Notes 454
27 Maintenance Awry – Chondrodysplasias and Achondroplasia 456
Achondroplasia 456
Ageing of Cartilage In Vivo 456
Genetic Disorders of Collagen Metabolism 458
Cartilage Anomaly (Can) Mice 458
Achondroplasia (ac/ac) in Rabbits 459
Achondroplasia (cn/cn) in Mice 460
Achondroplasia in Humans: FGFR3 460
Fgf18 460
Chondrodysplasia (Cho) in Mice 461
Sprouty Mice 461
Brachymorphic (bm) Mice 462
Nanomelia (nm) Domestic Fowl 463
Induced Micromelia 464
Metabolic Regulation and Stability of Differentiation 464
Notes 465
28 Restarting Mammalian Articular Chondrocytes 468
Mammalian Articular Chondrocytes In Vitro 468
A Role for Oxygen 469
Responsiveness to Environmental Signals 471
Mechanisms of Articular Cartilage Repair 475
Dividing Again In Vitro 475
Cartilage Repair After Culture In Vitro 477
Dividing Again In Vivo 478
DNA Synthesis and Cell Division 478
Osteotomy and Trauma 478
Transcription Factor 479
Notes 479
29 Repair of Fractured Long Bones and Regeneration of Growth Plates 482
A Brief History of Fracture Repair 482
Source of the Cells for Repair 482
Standardising the Fracture 483
Motion 483
Nonunions and Persistent Nonunions 484
Growth Factors and Fracture Repair 486
Bmps 488
Jump-Starting Repair 488
Regeneration of Growth Plates in Rats, Opossums and Humans 489
Notes 490
X. Growing Together and Growing Apart 492
30 Initiating Skeletal Growth 494
What Is Growth? 494
Numbers of Stem Cells 494
Cell Movement and Cell Viability 495
Epithelia, Fgf/FgfR2 and Mesenchymal Cell Proliferation 496
Metabolic Regulation 496
Creeper (cp) Fowl 496
Tibia/Fibula 496
Competing for Mesenchyme 497
Growth Retardation 499
A Growth Inhibitor 499
Mechanical Stimulation and Chondroblast Differentiation and Growth 499
Mechanical Stimuli and Metabolic Activity 500
Transduction of Mechanical Signals 501
Cellular Tensegrity 502
Membrane Potential 502
Skeletal Responses Mediated by camp 502
Matrix Synthesis and Condensation 503
Hormones 503
cAMP and Prechondroblast Proliferation 503
Long Bones in Chick Embryos 503
Mammalian Condylar Cartilage 504
Notes 505
31 Growth and Morphogenesis of Long Bones 506
Fundamental Form 506
Polarised Secretion 507
Long-Bone Growth 507
Growth Plates 510
Growth-Plate Dynamics 512
New Cells, Bigger Cells and Matrix 512
Cell Proliferation 512
Sources of Cells in Birds and Mammals 512
Regulation of Growth by Clones and by Timing 515
Hormonal Involvement 515
MicroRNAs 516
Growth at Opposite Ends of Long Bones 516
Diurnal and Circadian Rhythms 517
Rhythms Are Under Hormonal Control 517
The Periosteum and Regulation of the Growth Plate 517
Pig Mandibular Periostea 518
Periostea of Long Bones of Japanese Quail 519
Periosteal Sectioning 519
Chickens 519
Rodents 519
Rabbits 520
Feedback Control 520
Notes 521
32 Long Bone Growth: A Case of Crying Wolff? 522
Wolff, Von Meyer or Roux 522
Response to Pressure 524
Continuous or Intermittent Mechanical Stimuli 524
Scaling and Variation: When Wolff Meets the Dwarfs 525
Rats as Scaled-up Mice 525
Gravity 527
Prolonged Bed Rest 528
Transduction of Mechanical Stimuli 528
Notes 529
XI. Staying Apart 532
33 The Temporomandibular Joint and Cranial Synchondroses 534
MAMMALIAN TEMPOROMANDIBULAR JOINTS 534
Mechanical Forces 535
The Condylar Process 535
The Angular Process 537
Diet 538
Other Functional Approaches and the Functional Matrix 538
Cranial Synchondroses 540
As Pacemakers 540
Limited Growth Potential 544
As Adaptive 545
Notes 545
34 Sutures and Craniosynostosis 548
Sutural Growth as Secondary and Adaptive 548
Working with the Functional Matrix 553
Sutural Cartilage 553
The Dura 555
Craniosynostosis 556
Msx2 and Ameloblastin 557
Fgf Receptors 558
Sutural Growth 558
Sutural Fusion 558
Twist and Periostin 559
Notes 560
XII. Limb Buds 562
35 The Mesodermal Limb Field and the Apical Epithelial Ridge 564
Introduction 564
The Mesodermal Limb Field and Limb Bud Mesenchyme 564
Regulation 566
Ectodermal/Epithelial Responsiveness 569
Limb Field Mesoderm/Limb Bud Mesenchyme Specifies Limb Identity as Fore- or Hind Limb 569
Molecular Specification of Fore- and Hind Limbs 570
Positioning Paired Appendages 570
Hoxc8 cis-regulation 570
Specification of Fore- and Hind Limbs 571
Tbx4 and Tbx5 571
Early Differences Between Fore- and Hind Limb Buds 572
Tgfs 572
Roles for the Epithelium Associated with the Limb Field 573
Limb-Bud Growth 573
Cell Proliferation 574
Suppressing the Flank 574
Mitotic Rate in Limb Mesenchyme 574
Proximo-Distal Patterning of the Limb Skeleton 575
Limb Bud Mesenchyme Maintains the AER 575
Apical Epidermal Maintenance Factor (AEMF) 575
The Posterior Necrotic Zone (PNZ) 576
Specificity of Limb-Bud Epithelium 577
Distal and Proximal Limb Bud Mesenchyme 578
A Mechanical Role for the Epithelium? 579
Notes 580
36 Adding or Deleting an Apical Epithelial Ridge 582
Regeneration of the Apical Epithelial Ridge 582
Experimental Removal of the Apical Epithelial Ridge 583
Failure to Maintain an AER: Wingless (wl) Mutants 584
Mutual Interaction and Molecular Bases 585
Molecular Bases 586
Experimental Addition of an AER 586
Mutants with Duplicated Limbs 586
An Enlarged AER 587
Duplicating the AER 587
Narrow or Subdivided AERs 590
Polyphalangy and Extra Joints 590
Polyphalangy as Normal Phenotype 590
Polyphalangy as Variant Phenotype 591
Paraphalanges 592
Notes 593
37 Limb Buds in Limbed and Limbless Tetrapods 596
Apical Epithelial Ridges Across the Tetrapods 596
Anuran Amphibians 596
Urodele Amphibians 597
Reptiles 597
Mammals 597
Mice 597
Chick–Mouse Chimaeras 598
Humans 598
Limbless Tetrapods 599
Evolutionary Patterns 599
Gaining Limbs Back: ReEvolution of Limbs 600
Amphisbaenians (Worm Lizards) 600
Ecological Correlates of Limblessness 601
The Developmental Basis of Limblessness in Snakes and Legless Lizards 603
Inability to Maintain an AER 604
Notes 605
XIII. Limbs and Limb Skeletons 608
38 Axes and Polarity of Limb Buds and Limbs 610
Establishing Axes and Polarity 610
The A–P Axis and the ZPA 610
A Role for Fgf2 612
dHand and Shh 612
Hypodactyly, Oligozeugodactyly and Shh 613
Wnts and Fgf5, 8 and 10 613
ZPAs Abound 614
D–V Polarity 614
P–D Polarity and the Progress Zone 614
Early Specification Versus a Progress Zone 614
P–D Polarity and Amphibian Limb Regeneration 615
Connecting D–V and P–D Polarity 615
Thalidomide and Limb Defects 616
Time of Action 617
Mode of Action 618
Notes 619
39 Patterning and Shaping Limb Buds and Limb Skeletons 620
Morphogenesis and Growth 620
Apoptosis 620
Posterior and Anterior Necrotic Zones (PNZ, ANZ) 621
Timing of Apoptosis 621
Role of Apoptosis 622
Interdigital Apoptosis 622
A Role for BmpR1 623
Interdigital Apoptosis in Limb Buds of Mouse Embryos 623
The Opaque Patch 625
Cell Adhesion, Morphogenesis and Growth: talpid (ta) Mutant Fowl 625
talpid2 (ta2) 625
talpid3 (ta3) 626
Notes 628
40 Before Limbs There Were Fins 630
FINS AS PAIRED AND UNPAIRED APPENDAGES 630
Median Unpaired Fins in Teleost Fish 630
Lifestyle and Median Fins 631
Developmental Origins of Median Fins: Mesodermal or Neural Crest? 633
Fin Rays and Scales 633
Evolutionary Origins of Median Fins 634
Coelacanths Make a Contribution 634
Paired Fins 635
Three Pairs of Paired Fins 636
Development of Paired Fins 637
Fin Buds and Fin Folds 637
Skeletons of Paired Fins 638
Growth of Fin Rays 638
Fin Ray Regeneration 640
Retinoic Acid and Fin Development 642
Retinoic Acid and Regeneration 643
A Retinoic Acid–Shh Link 643
More on Fin Regeneration 643
Pelvic Fin Loss 644
Fins into Limbs 645
Structure and Function 645
Extant Phylogenetic Bracketing 645
From Many to Fewer Digits 646
Notes 647
XIV. Backbones and Tails 650
41 Vertebral Chondrogenesis: Cell Differentiation and Morphogenesis 652
Self-Differentiation or Induction? 652
Morphogenesis 653
Spinal Ganglia and Vertebral Morphogenesis 655
Chondrogenesis In Vitro 655
Spontaneous Chondrogenesis? 656
Cell Division and Cell Death 658
Notes 658
42 Relationships Between Notochord and Vertebral Cartilage 660
Integrity of Notochord/Spinal Cord and Vertebral Morphogenesis 660
For How Long Do Notochord and Spinal Cord Interact with Sclerotomal Mesenchyme? 661
Can Cartilage Form from Dermomyotome or from Lateral-Plate Mesoderm? 661
The Search for the Magic Bullet 662
Cartilage Cells as Cartilage Inducers 664
Chondrocyte Extracellular Matrix 664
Notochord and Spinal Cord Extracellular Matrices 665
Glycosaminoglycans 665
Collagens 666
Functions of Notochord and Spinal Cord Matrix Products 667
The Magic Bullets 668
Pax1 and Pax9 668
Shh 668
Bmp4, Msx1 and Msx2 669
Conclusions on Initiation of Vertebral Chondrogenesis 669
Notochord as a Type of Cartilage 669
A Transformational Series 670
Similar Kinds 670
Notochord Structure 670
Notochord, Chordoid and Chondroid 671
Notochord and Cartilage 671
Notes 674
43 Tail Buds, Tails and Taillessness 676
What Is a Tail? 676
Tail Buds 676
The Ventral Epithelial Ridge 678
Tbx Genes 679
Tail Growth 680
Genes and Environment 680
Temperature 682
Experiments with Mice 682
Temperature-Induced Change in Vertebral Number: Meristic Variation 683
Natural Variation and Adaptive Value of Vertebral Number 683
Studies with Teleost Fish 684
Studies with Chick Embryos 685
Studies with Mammals 685
Temperature Plus… 685
Taillessness 686
And Thereby Hangs a Tail 686
Fish Tails 687
Lizards’ Tails: Autotomy 688
Notes 689
XV. Evolutionary Skeletal Biology 690
44 Variation and Variability 692
Variation and Variability 692
Variation in a Single Character 693
Variability and Constraint 693
Hypotheses Tested by the Study of Variation and Variability 695
Vestigial Digits Enhance Variation 695
Variability and Variation Varies by Skeletal System 695
Diet and Altitude Influence Skull Variation 695
Shared Developmental Change Results in Convergent Variation 696
Pattern Variation in Limbs, Caudal Fins, Beaks and Jaws 696
Limbs 696
Caudal Fins 697
Beaks of Darwin’s Finches and Jaws of Cichlid Fishes 697
Metamorphosis 699
Miniaturisation as a Source of Variation 699
Urodele and Anuran Amphibians 700
Teleost Fish 701
The Smallest Teleost Fish 701
Heterochrony 702
Heterochrony as Concept 702
Positive Allometry 703
Heterochrony as Process 703
Coupling and Uncoupling Dermal and Endochondral Ossification 706
Heterochrony and Primate Skeletal Evolution 707
Notes 710
45 Variation Outside the Norm: Neomorphs and Atavisms 712
Neomorphs 712
Origin of the Term/Concept 712
Mode of Development and Phylogenetic Retention 712
Furculae in Birds 713
The Preglossale of the Common Pigeon 713
Secondary Jaw Articulations in Birds 713
A Boid Intramaxillary Joint 714
Regenerated Joints 714
Neomorphs or Vestiges 715
Limb Rudiments in Mysticete Whales 715
Levels of Analysis and Identification of Neomorphic Features 716
Digits 716
Turtle Shells 717
Evolutionary History 717
Development 719
Novel Modes of Ossification: Osteoderms 720
Osteoderms in Reptiles 720
Development 720
Evolutionary Record 721
Osteoderms in Xenarthrans 722
Atavisms 723
Taxic Atavisms 724
Neomorph or Atavism? 724
Homeotic Genes/Transformation and Variation Outside the Norm 724
Hox Genes 724
Homeotic Transformation of Vertebrae 725
Notes 726
References 728
Index 888
Preface
Brian K. Hall
The first few paragraphs and bullet list are taken pretty much verbatim from the Preface to Developmental and Cellular Skeletal Biology (Hall, 1978a in references). Their durability attests to the wide number of disciplines for which the skeleton was and remains central.
The skeleton has fascinated humankind ever since it was realised that, aside from one or several sets of genes, bare bones are our only bequest to posterity. The skeleton is more than an articulated set of bones, however. In human skeletons, the following hold true:
• three-dimensional conformation establishes the basis of our physical appearance;
• formation and rate of differentiation determine our shape and size at birth;
• postnatal growth orders us among our contemporaries and sets our final stature; while its
• decline in later life is among the primary causes of loss of the swiftness and agility of youth.
Not surprisingly, the skeleton is a central focus of many scientific and biomedical disciplines and investigations.
For developmental or cell biologists, the skeleton provides an ideal model for studies of gene action in normal and abnormal development, cell differentiation, morphogenesis, polarised growth, epithelial–mesenchymal interactions, programmed cell death and the role of the extracellular matrix. The skeleton supplies geneticists with a permanent record of the vicissitudes of its growth, whereby the phenotypic expression of genetic abnormalities can be studied. Orthopaedic surgeons earn a livelihood from correcting abnormalities and breaks, while orthodontists and oral surgeons use their knowledge of bone resorption to correct the position of teeth displaced consequent to alveolar bone dysfunction. Physiologists, biochemists and nutritionists are concerned with the skeleton’s store of calcium and phosphorus and its response to vitamins and hormones, while haematologists find that the skeleton houses the progenitors of the blood cells. Pathologists endeavour to understand the disease states that result from abnormalities in skeletal cellular differentiation or function; surgeons want to prevent formation of skeletal tissues in the wounds that bear witness to their work. Vertebrate palaeontologists make their living from the analysis of the skeletons of extinct taxa. Veterinarians, physical anthropologists, radiographers, forensic scientists … the list goes on.
Bones come in all shapes and sizes. There are long bones, flat bones, curved bones, bones of irregular and geometrically indefinable shapes, large and small bones. Bones exhibit bumps, ridges, grooves, holes and depressions where they articulate with other bones or attach to tendons and ligaments, and where nerves and blood vessels course through them. Some bones and cartilages arise within the skeleton and are integral parts of it. Others arise outside the skeleton, some as sesamoids or ossifications within tendons or ligaments, others as pathological ossifications in what otherwise would be soft tissues. Bones and cartilages may develop during embryonic or fetal life, in larval stages or in adulthood – often late in adulthood – during normal ontogeny, wound repair or regeneration. Bones modify themselves in response to injury, disease or parasitic infection, in the aftermath of surgery, as a defensive response to predators, as a consequence of domestication or hibernation and through evolutionary adaptations.
The previous edition of this book was published in 2005. It and this second edition are concerned with the nature of bones and cartilages and the cells that make them: how skeletal cells, tissues and organs are made, develop and age, and how they evolved. In the preface to the first edition I set out some 20 questions concerning skeletal development and 11 questions concerning skeletal evolutionA. I will not list those questions again. Many have been answered in the intervening 10 years (the literature for the first edition went into 2004), but many have not. The aim in this as in the previous edition is to analyse and evaluate studies of the development, growth and evolution of the skeleton and of skeletal tissues to provide a synthesis of the field of Developmental and Evolutionary Skeletal Biology.
Organisational Changes
I have kept the same organisation in this edition as in the first. Every chapter has been revised and updated extensively and the single chapter in Part XV (Evolutionary Skeletal Biology) is now two (44 and 45) devoted to the origin of skeletal variation and organismal variability in producing changes to the skeleton. Because the flow is the same, I will not provide a detailed outline of the organisation of the book here. Rather, I (a) have added introductions to each of the 15 parts that outline the topics of the chapters in each of those parts, and (b) summarise below (and on the back cover) some of the major advances in understanding.
The literature from 2004 to around August 2014 has been analysed and integrated into the book. In doing so I have reduced the number of references by 8% to 6,182. I was able to do this by including only key references to older studies by individuals or from individual laboratories, marking those with an asterisk in both the reference list and in the text. For more complete lists of earlier studies, refer to the first edition. Major reviews also are identified with an asterisk. Additionally, and for ease of working from the reference list, I have added the chapter(s) in which a particular reference is cited in square brackets at the end of the citation in the reference list. A random example is: * Anderson, H. C. (1985). Matrix vesicle calcification: Review and update. In Bone and Mineral Research/3 (W. A. Peck, ed.), pp. 109–149. Elsevier Science Publishers B. V., Amsterdam. [22].
Most figures from the first edition have been retained and 45 new figures have been added. Major terms and concepts are placed in bold or in italics in the text. As in the first edition, references, comments and elaborations (and a few asides) are in endnotes at the end of each chapter. A detailed single subject and taxonomic index is provided. Acknowledgements to individuals who generously commented on sections of text are included as endnotes in the appropriate chapters.
Conceptual Changes
The back cover contains a list of some of the changes in content from the first edition. Here I highlight some of the substantive changes in our understanding of skeletal development and evolution from research over the past decade.
We now have an appreciation of the integrated and coordinated functioning of the vascular, haematopoietic and skeletal systems in whole organism physiology.
Although known since Thomas Huxley’s time (Huxley, 1859), our understanding of the fundamental differences in vertebral development between teleost fish and tetrapods has been expanded greatly. In fish, vertebral development is initiated by mineralisation of the sheath of the notochord, which also is responsible for vertebral segmentation. In tetrapods, vertebral development is initiated by chondrogenesis of sclerotomal cells, and segmentation is a function of the sclerotomal mesenchyme. One consequence is that relationships among notochord, chondroid and cartilage have been reevaluated in the context of whether notochord is a form of cartilage.
The evolutionary origins of cartilage have been reinterpreted on the basis of new phylogenetic, cellular and genetic data, including the importance of gene regulatory networks in chondrogenesis (and osteogenesis).
Dedifferentiation of osteoblasts has been identified as the source of blastemal cells in regeneration of fin rays in zebrafish.
Recent data on a mesodermal rather than neural crest origin of teleost fin rays and scales are analysed. One of many consequences is a reevaluation of the proposal by Smith and Hall (1993) of the recognition of the exoskeleton and the endoskeleton on the basis of their origin in neural crest or mesoderm, respectively. The division into exo- and endo- remains valid, but not on the basis of germ layer of origin.
There is increased discussion of dinosaur bone based on palaeohistology and evaluation of whether skeletal growth is ever indeterminate.
Discovery of ‘avian’ secondary cartilage in dinosaurs is discussed in relation to dinosaur origins of birds and the evolution of secondary chondrogenesis.
There has been expanded treatment of stem cells in embryos and adults, including mesenchymal stem cells and their use in genetic engineering of cartilage, and the concept of the stem cell niche.
There is enhanced discussion of resolution to hurdles associated with in vitro culture of articular cartilage and repair in vivo.
Since 1968 my research has been supported continuously by the National Research Council (NRC) and then the Natural Sciences and Engineering Research Council (NSERC) of Canada (grants A5056 and 257447-02). I have also had additional support, from time to time, from the Research Development Fund and Killam Trust of Dalhousie University and from funds associated with the George S. Campbell Chair in Biology, a University Research Professorship, the Victoria General Hospital (Halifax), the Medical Research Council (Canada), the Canadian Institutes of Health Research, the Killam Trust of the Canada Council for the Arts, and the US National Institutes of Health (NIH; grant 45344). To all these agencies, my heartfelt thanks. I am enormously grateful to Pat Gonzalez, Karen East and...
| Erscheint lt. Verlag | 23.12.2014 |
|---|---|
| Sprache | englisch |
| Themenwelt | Medizinische Fachgebiete ► Chirurgie ► Unfallchirurgie / Orthopädie |
| Naturwissenschaften ► Biologie ► Genetik / Molekularbiologie | |
| Naturwissenschaften ► Biologie ► Zellbiologie | |
| Naturwissenschaften ► Biologie ► Zoologie | |
| Technik | |
| ISBN-10 | 0-12-416685-7 / 0124166857 |
| ISBN-13 | 978-0-12-416685-1 / 9780124166851 |
| Haben Sie eine Frage zum Produkt? |
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