Hall Bones and Cartilage

Developmental and Evolutionary Skeletal Biology
1. Auflage 2005
ISBN: 978-0-08-045415-3
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, 792 Seiten

Bones and Cartilage provides the most in-depth review ever assembled on the topic. It examines the function, development and evolution of bone and cartilage as tissues, organs and skeletal systems. It describes how bone and cartilage is developed in embryos and are maintained in adults, how bone reappears when we break a leg, or even regenerates when a newt grows a new limb, or a lizard a tail. This book also looks at the molecules and cells that make bones and cartilages and how they differ in various parts of the body and across species. It answers such questions as 'Is bone always bone? 'Do bones that develop indirectly by replacing other tissues, such as marrow, tendons or ligaments, differ from one another? 'Is fish bone the same as human bone? 'Can sharks even make bone? and many more.* Complete coverage of every aspect of bone and cartilage* Full of interesting and unusual facts* The only book available that integrates development and evolution of the skeleton* Treats all levels from molecular to clinical, embryos to evolution* Written in a lively, accessible style* Extensively illustrated and referenced* Integrates analysis of differentiation, growth and patterning* Covers all the vertebrates as well as invertebrate cartilages* Identifies the stem cells in embryos and adults that can make skeletal tissues

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.

Zielgruppe

Academic/professional/technical: Research and professional

Autoren/Hrsg.

Hall, Brian K.

Inhaltsverzeichnis

1;Bones and Cartilage: Developmental and Evolutionary Skeletal Biology;2
1.1;Epigraph;3
1.2;Contents;6
1.3;Preface;20
1.4;Abbreviations;24
1.5;Part I Skeletal Tissues;30
1.6;Chapter 1 Types of Skeletal Tissues;32
1.6.1;BONE;33
1.6.2;CARTILAGE;34
1.6.3;DENTINE;34
1.6.4;ENAMEL;36
1.6.5;INTERMEDIATE TISSUES;37
1.6.5.1;Cementum;37
1.6.5.2;Enameloid;39
1.6.5.3;Chondroid and chondroid bone;40
1.6.6;BONE OR CARTILAGE;40
1.6.7;NOTES;41
1.7;Chapter 2 Bone;42
1.7.1;DISCOVERY OF THE BASIC STRUCTURE OF BONE;42
1.7.2;CELLULAR BONE;44
1.7.3;OSTEOCYTES;45
1.7.4;INTRAMEMBRANOUS VERSUS ENDOCHONDRAL BONE;46
1.7.4.1;Embryonic origins;46
1.7.4.2;Other modes;46
1.7.4.3;Metabolic differences;47
1.7.4.4;Morphogenetic differences;47
1.7.5;OSTEONES;48
1.7.6;GROWTH;50
1.7.7;REGIONAL REMODELING;50
1.7.8;AGEING;51
1.7.8.1;Osteones over time;52
1.7.9;ACELLULAR BONE;53
1.7.9.1;Caisson disease and abnormal acellular bone in mammals;53
1.7.9.2;Acellular bone in teleost fishes;53
1.7.9.2.1;Development;54
1.7.9.2.2;Resorption;54
1.7.9.2.3;Repair of fractures;55
1.7.9.2.4;Ca++ regulation;55
1.7.9.3;Aspidine;59
1.7.10;BONE IN CARTILAGINOUS FISHES (SHARKS AND RAYS);59
1.7.11;NOTES;59
1.8;Chapter 3 Cartilage;62
1.8.1;TYPES;62
1.8.2;CHONDRONES;63
1.8.3;CARTILAGE GROWTH;64
1.8.4;CARTILAGE CANALS;65
1.8.5;SECONDARY CENTRES OF OSSIFICATION;65
1.8.6;ELASTIC CARTILAGE;68
1.8.6.1;Elastic fibres;68
1.8.6.2;The cells;68
1.8.6.3;Elastic cartilage intermediates;70
1.8.7;SHARK CARTILAGE;70
1.8.7.1;Development and mineralization;70
1.8.7.2;Growth;71
1.8.7.3;Inhibition of vascular invasion;71
1.8.8;LAMPREYS;71
1.8.8.1;Mucocartilage;72
1.8.8.2;Lamprin;72
1.8.8.3;Mineralization;73
1.8.9;HAGFISH;74
1.8.10;NOTES;74
1.9;Part II Natural Experiments;78
1.10;Chapter 4 Invertebrate Cartilages;80
1.10.1;CHONDROID, CARTILAGE OR NEITHER;80
1.10.2;ODONTOPHORE CARTILAGE IN THE CHANNELED WHELK, BUSYCON CANALICULATUM;81
1.10.3;BRANCHIAL (GILL BOOK) CARTILAGE IN THE HORSESHOE CRAB, LIMULUS POLYPHEMUS;81
1.10.4;CRANIAL CARTILAGES IN SQUID, CUTTLEFISH AND OCTOPUSES;82
1.10.4.1;Composition of the extracellular matrix;82
1.10.4.1.1;Glycosaminoglycans (GAGs);82
1.10.4.1.2;Collagens;82
1.10.5;TENTACULAR CARTILAGE IN POLYCHAETE ANNELIDS;84
1.10.6;LOPHOPHORE CARTILAGE IN AN ARTICULATE BRACHIOPOD, TEREBRATALIA TRANSVERSA;85
1.10.7;MINERALIZATION OF INVERTEBRATE CARTILAGES;85
1.10.8;CARTILAGE ORIGINS;85
1.10.9;NOTES;91
1.11;Chapter 5 Intermediate Tissues;93
1.11.1;CHONDROID AND CHONDROID BONE;95
1.11.2;MODULATION AND INTERMEDIATE TISSUES;95
1.11.3;CARTILAGE FROM FIBROUS TISSUE AND METAPLASIA;97
1.11.4;METAPLASIA OF EPITHELIAL CELLS TO CHONDROBLASTS OR OSTEOBLASTS;97
1.11.4.1;Chondroid;98
1.11.4.2;Teleosts;98
1.11.4.3;Mammals;99
1.11.5;CHONDROID BONE;100
1.11.5.1;Teleosts;100
1.11.5.2;Mammals;100
1.11.5.3;Chondroid bone and pharyngeal jaws;101
1.11.6;TISSUES INTERMEDIATE BETWEEN BONE AND DENTINE;103
1.11.6.1;Dentine;104
1.11.6.2;Cementum;105
1.11.7;ENAMELOID: A TISSUE INTERMEDIATE BETWEEN DENTINE AND ENAMEL;106
1.11.8;NOTES;110
1.12;Chapter 6 An Evolutionary Perspective;112
1.12.1;FOSSILIZED SKELETAL TISSUES;112
1.12.2;ALL FOUR SKELETAL TISSUES ARE ANCIENT;113
1.12.3;EVOLUTIONARY EXPERIMENTATION;115
1.12.3.1;Intermediate tissues in fossil agnatha;115
1.12.4;DINOSAUR BONE;116
1.12.5;DEVELOPING FOSSILS;117
1.12.6;PROBLEMATICA;117
1.12.7;PALAEOPATHOLOGY;118
1.12.8;CONODONTS;119
1.12.9;NOTES;120
1.13;Part III Unusual Modes of Skeletogenesis;122
1.14;Chapter 7 Horns and Ossicones;124
1.14.1;HORNS;124
1.14.2;DISTRIBUTION OF HORNS AS ORGANS;125
1.14.2.1;Bovidae;125
1.14.2.2;Rhinos;127
1.14.2.3;Titanotheres;128
1.14.2.4;Pronghorn antelopes;128
1.14.2.5;Giraffes;129
1.14.3;HORN AS A TISSUE;130
1.14.4;DEVELOPMENT AND GROWTH OF HORNS;130
1.14.5;NOTES;131
1.15;Chapter 8 Antlers;132
1.15.1;ANTLERS;132
1.15.1.1;Size and absence;132
1.15.2;INITIATION OF ANTLER FORMATION;133
1.15.2.1;Pedicle formation;133
1.15.2.2;The antler bud and dermal–epidermal interactions;134
1.15.3;HORMONAL CONTROL OF PEDICLE DEVELOPMENT AND GROWTH;135
1.15.4;ANTLER REGENERATION;135
1.15.4.1;The shedding cycle;135
1.15.5;HISTOGENESIS OF ANTLERS;136
1.15.5.1;White-tailed deer, American elk, European fallow and roe deer;137
1.15.5.2;Rocky Mountain mule deer;139
1.15.5.3;Sika deer;139
1.15.6;HORMONES, PHOTOPERIOD AND ANTLER GROWTH;139
1.15.6.1;Sika deer Photoperiod and testosterone;139
1.15.6.2;Parathyroid hormone and calcitonin;142
1.15.7;NOTES;142
1.16;Chapter 9 Tendons and Sesamoids;144
1.16.1;TENDONS AND SKELETOGENESIS;144
1.16.1.1;Fibrocartilage in tendons;145
1.16.1.2;Rodent Achilles tendons;146
1.16.1.3;Ossification of avian tendons;146
1.16.1.4;Formation and composition of tendon fibrocartilages;146
1.16.1.4.1;Condensation;146
1.16.1.4.2;Scleraxis;147
1.16.1.4.3;Composition;148
1.16.2;SESAMOIDS;148
1.16.2.1;Amphibians;149
1.16.2.2;Reptiles;150
1.16.2.3;Birds;150
1.16.2.4;Teleosts;151
1.16.3;NOTES;151
1.17;Part IV Stem Cells;154
1.18;Chapter 10 Embryonic Stem Cells;156
1.18.1;STEM CELLS;156
1.18.2;SET-ASIDE CELLS;158
1.18.3;STEM CELLS FOR PERIOSTEAL OSTEOGENESIS IN LONG BONES;160
1.18.4;MODULATION OF SYNTHETIC ACTIVITY AND DIFFERENTIATIVE PATHWAYS OF CELL POPULATIONS;162
1.18.4.1;Fibroblast–chondroblast modulation;162
1.18.4.2;Modulation of glycosaminoglycan synthesis;162
1.18.5;MODULATION OF SYNTHETIC ACTIVITY AND DIFFERENTIATIVE PATHWAYS IN SINGLE CELLS;163
1.18.5.1;Degradative activity;163
1.18.6;NOTES;165
1.19;Chapter 11 Stem Cells in Adults;167
1.19.1;FIBROBLAST COLONY-FORMING CELLS;167
1.19.2;OSTEOGENIC PRECURSOR CELLS;168
1.19.2.1;Clonal analysis;169
1.19.2.2;Lineages of cells;169
1.19.2.3;Dexamethasone;169
1.19.3;EPITHELIAL INDUCTION OF ECTOPIC BONE;170
1.19.3.1;Epithelial cell lines;171
1.19.4;NOTES;173
1.20;Part V Skeletogenic Cells;176
1.21;Chapter 12 Osteo- and Chondroprogenitor Cells;178
1.21.1;IDENTIFYING OSTEO- AND CHONDROPROGENITOR CELLS;179
1.21.1.1;Execrable terminology;179
1.21.1.2;Features;179
1.21.1.3;Cell cycle dynamics;179
1.21.2;BIPOTENTIAL PROGENITOR CELLS FOR OSTEOGENESIS AND CHONDROGENESIS;180
1.21.2.1;Bipotential cell populations or bipotential cells?;180
1.21.2.2;Uncovering bipotentiality;180
1.21.2.3;Discovering bipotentiality;181
1.21.2.3.1;Biochemical and metabolic markers;181
1.21.2.3.2;Collagen types;182
1.21.2.3.3;The tumor suppressor gene p53;182
1.21.3;CONDYLAR CARTILAGE ON THE CONDYLAR PROCESS OF THE MAMMALIAN DENTARY;184
1.21.3.1;Histodifferentiation and scurvy;184
1.21.3.2;One or two cell populations;185
1.21.3.3;Evidence against bipotentiality;185
1.21.3.4;Evidence supporting bipotentiality;186
1.21.3.5;All or some?;188
1.21.4;SECONDARY CARTILAGE ON AVIAN MEMBRANE BONES;188
1.21.5;NOTES;193
1.22;Chapter 13 Dedifferentiation Provides Progenitor Cells for Jaws and Long Bones;195
1.22.1;CONDYLAR CARTILAGE OF THE MAMMALIAN TEMPOROMANDIBULAR JOINT;195
1.22.1.1;The temporomandibular joint;195
1.22.1.2;Hypertrophic chondrocytes survive;195
1.22.1.3;Hypertrophic chondrocytes transform to osteoprogenitor cells;196
1.22.2;MECKEL’S CARTILAGE;197
1.22.2.1;Mammalian Meckel’s;197
1.22.2.1.1;Prx-1, Prx-2;202
1.22.2.1.2;Alx-3;205
1.22.2.1.3;Ptx-1;205
1.22.3;DEDIFFERENTIATION DURING ENDOCHONDRAL BONE FORMATION;205
1.22.3.1;Rodent ribs;206
1.22.3.1.1;Mice;206
1.22.3.1.2;Rats;206
1.22.3.2;Appendicular long bones;207
1.22.3.2.1;Enzyme activity;207
1.22.3.2.2;Evidence from 3 H-thymidine-labeling and other approaches;208
1.22.3.3;Murine interpubic joints;210
1.22.4;NOTES;210
1.23;Chapter 14 Dedifferentiation and Urodele Amphibian Limb Regeneration;212
1.23.1;DEDIFFERENTIATION;212
1.23.1.1;Morphological dedifferentiation;213
1.23.1.2;Functional dedifferentiation;213
1.23.1.2.1;Hyaluronan;213
1.23.2;BLASTEMA FORMATION;215
1.23.2.1;Aneurogenic limbs;216
1.23.2.2;More than one cell fate;216
1.23.3;MYOBLAST AND CHONDROBLAST FATES;217
1.23.4;FACTORS CONTROLLING DEDIFFERENTIATION;218
1.23.4.1;Innervation;218
1.23.4.2;Aneurogenic limbs;218
1.23.4.3;Proliferation;218
1.23.4.4;Not the stump;219
1.23.4.5;Electrical signals?;220
1.23.4.6;Hox genes;220
1.23.4.7;FgfR-1 and FgfR-2;220
1.23.4.8;Radical fringe;220
1.23.5;WHY CAN’T FROGS REGENERATE?;221
1.23.5.1;Augmenting regeneration;223
1.23.6;FINGERTIPS OF MICE, MONKEYS AND MEN;224
1.23.6.1;Comparison with urodele limb regeneration;224
1.23.7;NOTES;225
1.24;Chapter 15 Cells to Make and Cells to Break;226
1.24.1;CLASTS AND BLASTS;226
1.24.2;RESORPTION;226
1.24.3;COUPLING BONE RESORPTION TO BONE FORMATION;227
1.24.4;COUPLING OSTEOBLASTS AND OSTEOCLASTS;227
1.24.5;SOME MOLECULAR PLAYERS;229
1.24.6;WHEN COUPLING GOES AWRY;230
1.24.7;TRAP-STAINING FOR OSTEOCLASTS;231
1.24.7.1;Mammalian osteoclasts;231
1.24.7.2;Teleost osteoclasts;232
1.24.8;NITRIC OXIDE – IT’S A GAS;232
1.24.9;PROGENITOR CELLS FOR OSTEOBLASTS AND OSTEOCLASTS;232
1.24.9.1;Japanese quail–domestic fowl chimaeras;234
1.24.10;OSTEOPETROSIS AND OSTEOCLAST ORIGINS;234
1.24.11;OSTEOCLAST–PHAGOCYTE–MACROPHAGE OR OSTEOCLAST–MONOCYTE LINEAGES?;237
1.24.11.1;Phagocyte/macrophage origin;237
1.24.11.2;Interleukins;238
1.24.11.2.1;IL-1;238
1.24.11.2.2;Osteogenesis;238
1.24.11.2.3;Chondrogenesis;238
1.24.11.2.4;IL-6;238
1.24.11.2.5;IL-10;238
1.24.11.3;Evidence against monocytes;239
1.24.11.4;Evidence for monocytes;239
1.24.12;CHONDROCLASTS AND OSTEOCLASTS;240
1.24.13;SYNOVIAL CELLS;240
1.24.14;NOTES;240
1.25;Part VI Embryonic Origins;244
1.26;Chapter 16 Skeletal Origins: Somitic Mesoderm;246
1.26.1;SOMITIC MESODERM AND THE ORIGIN OF THE VERTEBRAE;246
1.26.2;PARAXIAL MESODERM . SOMITES;247
1.26.3;SCLEROTOME FORMATION AND MIGRATION;247
1.26.4;RESEGMENTATION;249
1.26.5;SOMITIC CONTRIBUTION TO LIMB BUDS;251
1.26.5.1;Formation of muscle;251
1.26.5.2;Innervation and myogenesis;251
1.26.5.3;Signals to initiate a limb bud;252
1.26.6;A COMMENT ON PECTORAL GIRDLES;252
1.26.7;THE CLAVICLE: EVEN MORE SURPRISING;253
1.26.7.1;Humans;254
1.26.7.2;Other mammals;254
1.26.7.3;Mammals that lack clavicles;255
1.26.7.4;Birds;256
1.26.7.4.1;Wishbone or clavicles;256
1.26.8;NOTES;256
1.27;Chapter 17 Skeletal Origins: Neural Crest;259
1.27.1;DIFFERENT MESENCHYMES, SAME TISSUES;259
1.27.2;NEURAL CREST AS A SOURCE OF SKELETAL CELLS;260
1.27.3;EVIDENCE OF SKELETOGENIC POTENTIAL;260
1.27.3.1;Ablation and transplantation experiments;261
1.27.3.2;Marker experiments;262
1.27.3.2.1;3H-thymidine;262
1.27.3.2.2;Xenopus laevis–Xenopus borealis chimaeras;262
1.27.3.2.3;Quail–chick chimaeras;262
1.27.3.2.4;Genetic markers for murine neural crest;263
1.27.3.2.5;Information from mutants;265
1.27.4;REGIONALIZATION OF THE CRANIAL NEURAL CREST;268
1.27.5;THE VENTRAL NEURAL TUBE;268
1.27.6;MIGRATION OF NCC: THE ROLE OF THE ECM;269
1.27.7;NOTES;270
1.28;Chapter 18 Epithelial–Mesenchymal Interactions;272
1.28.1;URODELE AMPHIBIANS: CHONDROGENESIS;272
1.28.2;AVIAN MANDIBULAR SKELETON: CHONDROGENESIS AND OSTEOGENESIS;273
1.28.2.1;Isolated mesenchyme – chondrogenesis;276
1.28.2.2;Isolated mesenchyme – osteogenesis;276
1.28.2.3;Ruling out any role for Meckel’s cartilage;276
1.28.2.4;Molecular mechanisms;277
1.28.3;OSTEOGENESIS IN AVIAN MAXILLARY ARCH SKELETON;278
1.28.4;MAMMALIAN MANDIBULAR SKELETON;278
1.28.4.1;Endothelin-1 (Et-1);279
1.28.4.2;The Dlx gene family and craniofacial development;279
1.28.5;TELEOST MANDIBULAR ARCH SKELETON;281
1.28.5.1;Fgf;281
1.28.5.1.1;Hoxd-4 and retinoic acid;281
1.28.5.1.2;Limb development;281
1.28.5.1.3;Craniofacial development;281
1.28.5.1.4;Fish;282
1.28.5.2;Endothelin-1 (Et-1);282
1.28.5.3;Mutants;282
1.28.6;LATERAL LINE, NEUROMASTS AND DERMAL BONE;282
1.28.6.1;Hope from a single trout;282
1.28.7;TERATOMAS;283
1.28.7.1;Germ-layer combinations;283
1.28.8;MESENCHYME SIGNALS TO EPITHELIUM;284
1.28.9;SPECIFICITY OF EPITHELIAL–MESENCHYMAL INTERACTIONS;284
1.28.10;NOTES;285
1.29;Part VII Getting Started;288
1.30;Chapter 19 The Membranous Skeleton: Condensations;290
1.30.1;THE MEMBRANOUS SKELETON;290
1.30.2;CONGENITAL HYDROCEPHALUS (ch);292
1.30.3;CHARACTERIZING CONDENSATIONS;293
1.30.4;HOW CONDENSATIONS ARISE;295
1.30.4.1;Altered mitotic activity;295
1.30.4.2;Changing cell density;295
1.30.4.3;Aggregation and/or failure to disperse;296
1.30.4.3.1;Limb buds and limb regeneration;296
1.30.4.4;Molecular control;297
1.30.5;ESTABLISHING BOUNDARIES;298
1.30.5.1;Syndecan and tenascin;298
1.30.5.2;Fgfs;299
1.30.5.3;Wnt-7a;299
1.30.6;NOTES;299
1.31;Chapter 20 From Condensation to Differentiation;301
1.31.1;CONDENSATION GROWTH;301
1.31.1.1;Lessons from mutants;302
1.31.1.1.1;talpid3;302
1.31.1.1.2;bpH;303
1.31.2;ADHERE, PROLIFERATE AND GROW;303
1.31.2.1;Gap junctions;303
1.31.2.1.1;Limb-bud mesenchyme;303
1.31.2.1.2;Craniofacial mesenchyme;303
1.31.2.2;Transcription Factors and Hox genes;303
1.31.3;POSITION AND SHAPE;305
1.31.4;ESTABLISHING CONDENSATION SIZE;306
1.31.4.1;Bmps;306
1.31.4.2;Fibronectin;306
1.31.4.3;Hyaluronan;306
1.31.4.4;Extrinsic control;307
1.31.5;FROM CONDENSATION TO OVERT DIFFERENTIATION;307
1.31.5.1;The molecular cascades;309
1.31.5.1.1;Bmps;309
1.31.5.1.2;Tenascin and N-CAM;309
1.31.5.1.3;Runx-2;310
1.31.6;NOTES;311
1.32;Chapter 21 Skulls, Eyes and Ears: Condensations and Tissue Interactions;313
1.32.1;THE BONY SKULL;313
1.32.1.1;Avian skull development;314
1.32.1.2;Mammalian skull development;316
1.32.2;THE CARTILAGINOUS SKULL;317
1.32.2.1;Type II collagen;317
1.32.2.2;Otic, optic and nasal capsules;317
1.32.2.2.1;The otic vesicle;317
1.32.2.2.2;Morphogenesis;318
1.32.3;TYMPANIC CARTILAGES;319
1.32.4;SCLERAL CARTILAGE;320
1.32.4.1;Heterogeneity;320
1.32.4.2;Chondrogenic mesenchyme;320
1.32.4.3;Pigmented retinal epithelium (PRE);320
1.32.4.4;Morphogenesis;321
1.32.5;SCLERAL OSSICLES;322
1.32.5.1;Ossicle number;322
1.32.5.2;Scleral papillae;323
1.32.5.3;An epithelial–mesenchymal interaction;323
1.32.5.4;Scaleless mutant fowl;324
1.32.5.5;A role for tenascin?;324
1.32.6;NOTES;326
1.33;Part VIII Similarity and Diversity;328
1.34;Chapter 22 Chondrocyte Diversity;330
1.34.1;SEGREGATION FROM PRECURSORS;330
1.34.2;PERICHONDRIA;331
1.34.3;MORPHOGENETIC SPECIFICITY;332
1.34.4;CARTILAGES OF DIFFERENT EMBRYOLOGICAL ORIGINS;333
1.34.5;CHONDROCYTE HYPERTROPHY;334
1.34.6;TYPE X COLLAGEN;334
1.34.6.1;Discovery and regulation of synthesis;334
1.34.6.2;Syndromes and mutations;335
1.34.6.3;Type X does not always indicate hypertrophy;336
1.34.6.4;Regulation of chondrocyte hypertrophy;336
1.34.6.4.1;Tgf;337
1.34.6.4.2;Bmps;337
1.34.6.5;Type X and mineralization;338
1.34.6.5.1;Birds;338
1.34.6.5.2;Frogs;338
1.34.6.5.3;Rickets;338
1.34.7;MATRIX VESICLES;338
1.34.8;HYPERTROPHIC CHONDROCYTES AND SUBPERIOSTEAL OSSIFICATION;340
1.34.8.1;Brachypod (bpH ) in mice;340
1.34.8.1.1;Early changes;341
1.34.8.1.2;Fibulae;341
1.34.8.1.3;A role for Wnts;341
1.34.9;NOTES;343
1.35;Chapter 23 Cartilage Diversity;345
1.35.1;STERNAL CHONDROCYTES;345
1.35.1.1;Synthesis of collagen and glycosaminoglycan (GAG);345
1.35.1.2;Differential expression of type II collagen;345
1.35.1.3;Differential synthesis and organization of collagen types;345
1.35.1.4;Type X collagen and hypertrophy;347
1.35.1.5;Fibronectin;347
1.35.1.6;Nanomelia;347
1.35.2;TUMOUR INVASION;347
1.35.3;VASCULARITY;348
1.35.4;RESISTING VASCULAR INVASION;349
1.35.5;INHIBITORS OF ANGIOGENESIS AND VASCULAR INVASION;350
1.35.5.1;Vascular endothelial growth factor (Vegf);350
1.35.6;PTH-PTHrP;351
1.35.7;INTERPUBIC JOINTS AND THE TRANSFORMATION OF CARTILAGE TO LIGAMENT;351
1.35.7.1;Cartilage . ligament;353
1.35.7.2;Mediation by oestrogen and relaxin;354
1.35.8;NOTES;355
1.36;Chapter 24 Osteoblast and Osteocyte Diversity;357
1.36.1;OSTEOCYTIC OSTEOLYSIS;357
1.36.2;INITIATING OSTEOGENESIS IN VITRO FROM EMBRYONIC MESENCHYME;359
1.36.3;OSTEOGENIC CELLS IN VITRO;359
1.36.3.1;Folded periostea;361
1.36.3.2;Establishing isolated osteoblasts and initiating osteogenesis in vitro;362
1.36.3.2.1;Calvarial osteoblasts in vitro;362
1.36.3.2.2;Isolating subpopulations of calvarial osteogenic cells;363
1.36.3.2.3;Chondrogenesis from rodent and avian osteogenic cells;364
1.36.3.3;Clonal cultures;365
1.36.4;NOTES;365
1.37;Chapter 25 Bone Diversity;367
1.37.1;HETEROGENEITY OF RESPONSE TO SODIUM FLUORIDE;367
1.37.1.1;Enhanced proliferation and osteogenesis;367
1.37.1.2;Interaction with hormonal action;368
1.37.1.3;Osteoporosis;369
1.37.1.4;Chondrogenesis;369
1.37.1.5;Mineralization;369
1.37.1.6;Mechanical properties of bone;369
1.37.2;ALVEOLAR BONE OF MAMMALIAN TEETH;369
1.37.2.1;Origin;369
1.37.2.2;Physiology and circadian rhythms;369
1.37.3;PENILE AND CLITORAL CARTILAGES AND BONES;371
1.37.3.1;Os penis;373
1.37.3.2;Os clitoridis;373
1.37.3.3;Hormonal control;373
1.37.3.4;Digits and penile bones;374
1.37.3.5;Hoxd-12, Hoxd-13 AND POLYPHALANGY;374
1.37.4;OESTROGEN-STIMULATED DEPOSITION OF MEDULLARY BONE IN LAYING HENS;374
1.37.5;OESTROGEN-STIMULATED RESORPTION OF PELVIC BONES IN MICE;375
1.37.6;NOTES;376
1.38;Part IX Maintaining Cartilage in Good Times and Bad;378
1.39;Chapter 26 Maintaining Differentiated Chondrocytes;380
1.39.1;DIFFERENTIATED CHONDROCYTES;380
1.39.2;SYNTHESIS AND DEPOSITION OF CARTILAGINOUS EXTRACELLULAR MATRIX;381
1.39.2.1;Synthesis of chondroitin sulphate;381
1.39.2.2;Synthesis of type II collagen;382
1.39.3;SYNTHESIS OF COLLAGEN AND CHONDROITIN SULPHATE BY THE SAME CHONDROCYTE;382
1.39.3.1;Collagen gel culture;382
1.39.4;FEEDBACK CONTROL OF THE SYNTHESIS OF GLYCOSAMINOGLYCANS;382
1.39.4.1;Evidence from organ culture;382
1.39.4.2;Evidence from chondrocyte cell cultures;383
1.39.5;INTERACTIONS BETWEEN GLYCOSAMINOGLYCANS AND COLLAGENS WITHIN THE EXTRACELLULAR MATRIX;383
1.39.5.1;Synthesis of collagen and chondroitin sulphate are regulated independently;383
1.39.5.2;Hypertrophy;384
1.39.6;THE INTERACTIVE EXTRACELLULAR MATRIX;384
1.39.7;NOTES;385
1.40;Chapter 27 Maintenance Awry – Achondroplasia;387
1.40.1;GENETIC DISORDERS OF COLLAGEN METABOLISM;387
1.40.2;CARTILAGE ANOMALY (Can) IN MICE;388
1.40.3;ACHONDROPLASIA (Ac) IN RABBITS;389
1.40.4;ACHONDROPLASIA (Cn) IN MICE;389
1.40.4.1;FgfR-3;389
1.40.5;CHONDRODYSPLASIA (Cho) IN MICE;391
1.40.5.1;Sprouty;391
1.40.6;BRACHYMORPHIC (Bm) MICE;392
1.40.7;STUMPY (Stm) MICE;392
1.40.8;NANOMELIA (nm) IN DOMESTIC FOWL;392
1.40.9;INDUCED MICROMELIA;393
1.40.10;METABOLIC REGULATION AND STABILITY OF DIFFERENTIATION;393
1.40.11;NOTES;394
1.41;Chapter 28 Restarting Mammalian Articular Chondrocytes;396
1.41.1;MAMMALIAN ARTICULAR CHONDROCYTES IN VITRO;396
1.41.1.1;A role for oxygen;397
1.41.1.2;Responsiveness to environmental signals;397
1.41.2;MECHANISMS OF ARTICULAR CARTILAGE REPAIR;398
1.41.2.1;Dividing again in vitro;398
1.41.2.2;Dividing again in vivo;401
1.41.2.2.1;DNA synthesis vs. division;401
1.41.2.2.2;Osteotomy and trauma;402
1.41.3;NOTES;402
1.42;Chapter 29 Repair of Fractures and Regeneration of Growth Plates;404
1.42.1;A BRIEF HISTORY OF FRACTURE REPAIR;404
1.42.1.1;Standardizing the fracture;405
1.42.1.2;Motion;405
1.42.1.3;Non-unions and persistent non-unions;406
1.42.1.4;Growth factors and fracture repair;408
1.42.1.4.1;Bmps;409
1.42.1.5;Jump-starting repair;409
1.42.2;REGENERATION OF GROWTH PLATES IN RATS, OPOSSUMS AND MEN;409
1.42.3;NOTES;410
1.43;Part X Growing Together;412
1.44;Chapter 30 Initiating Skeletal Growth;414
1.44.1;WHAT IS GROWTH?;414
1.44.2;NUMBERS OF STEM CELLS;414
1.44.3;CELL MOVEMENT AND CELL VIABILITY;415
1.44.3.1;Epithelia and Fgf/FgfR-2;415
1.44.4;METABOLIC REGULATION;415
1.44.4.1;Creeper (cp) fowl;416
1.44.4.1.1;Tibia/fibula;416
1.44.4.1.2;Growth retardation;416
1.44.4.1.3;A growth inhibitor;417
1.44.5;MECHANICAL STIMULATION AND CHONDROBLAST DIFFERENTIATION/GROWTH;417
1.44.6;MECHANICAL STIMULI AND METABOLIC ACTIVITY;418
1.44.6.1;Transduction;418
1.44.6.2;Membrane potential;419
1.44.7;SKELETAL RESPONSES MEDIATED BY c419
1.44.7.1;Matrix synthesis and condensation;419
1.44.7.2;Hormones;419
1.44.7.3;Teeth and alveolar bone;420
1.44.7.4;Electrical stimulation;420
1.44.8;cAMP AND PRECHONDROBLAST PROLIFERATION;420
1.44.8.1;Long bones;420
1.44.8.2;Limb regeneration;421
1.44.8.3;Condylar cartilage;421
1.44.9;NOTES;421
1.45;Chapter 31 Form, Polarity and Long-Bone Growth;424
1.45.1;FUNDAMENTAL FORM;424
1.45.2;POLARITY;425
1.45.2.1;Polarized cells;425
1.45.3;LONG-BONE GROWTH;426
1.45.3.1;Growth plates;427
1.45.3.2;Growth-plate dynamics;428
1.45.3.2.1;New cells, bigger cells and matrix;428
1.45.3.2.2;Cell proliferation;429
1.45.3.2.3;Birds and mammals;431
1.45.3.2.4;Clones and timing;431
1.45.3.2.5;Hormonal involvement;432
1.45.3.3;Growth at opposite ends;432
1.45.3.4;Diurnal and circadian rhythms;432
1.45.3.4.1;Rhythms are under hormonal control;433
1.45.3.5;A role for the periosteum in regulation of the growth plate?;433
1.45.3.5.1;Periosteal sectioning;435
1.45.3.6;Feedback control;435
1.45.4;NOTES;436
1.46;Chapter 32 Long Bone Growth: A Case of Crying Wolff?;438
1.46.1;WOLFF, VON MEYER OR ROUX;438
1.46.2;RESPONSE TO PRESSURE;439
1.46.3;CONTINUOUS OR INTERMITTENT MECHANICAL STIMULI;440
1.46.4;SCALING AND VARIATION: WHEN WOLFF MEETS THE DWARFS;441
1.46.5;GRAVITY;441
1.46.6;TRANSDUCTION OF MECHANICAL STIMULI;443
1.46.7;NOTES;443
1.47;Part XI Staying Apart;446
1.48;Chapter 33 The Temporomandibular Joint and Synchondroses;448
1.48.1;THE MAMMALIAN TEMPOROMANDIBULAR JOINT (TMJ);448
1.48.1.1;Mechanical factors;449
1.48.1.1.1;The condylar process;449
1.48.1.1.2;The angular process;450
1.48.1.2;Diet;450
1.48.1.3;Other functional approaches;451
1.48.2;CRANIAL SYNCHONDROSES;452
1.48.2.1;As pacemakers;453
1.48.2.2;Limited growth potential;454
1.48.2.3;As adaptive;455
1.48.3;NOTES;456
1.49;Chapter 34 Sutures and Craniosynostosis;458
1.49.1;SUTURAL GROWTH AS SECONDARY AND ADAPTIVE;458
1.49.1.1;Alizarin;460
1.49.1.2;Working with the functional matrix;462
1.49.2;SUTURAL CARTILAGE;463
1.49.3;THE DURA;463
1.49.4;CRANIOSYNOSTOSIS;464
1.49.4.1;Msx-2;465
1.49.4.2;Fgf receptors;465
1.49.4.2.1;Sutural growth;465
1.49.4.2.2;Sutural fusion;466
1.49.5;NOTES;466
1.50;Part XII Limb Buds;470
1.51;Chapter 35 The Limb Field and the AER;472
1.51.1;THE MESODERMAL LIMB FIELD;472
1.51.2;ECTODERMAL RESPONSIVENESS;473
1.51.3;MESODERM SPECIFIES FORE- VS. HIND LIMB;474
1.51.4;ROLES FOR THE ECTODERM ASSOCIATED WITH THE LIMB FIELD;476
1.51.4.1;Limb-bud growth;479
1.51.4.1.1;Cell proliferation;479
1.51.4.1.2;Suppressing the flank;479
1.51.4.1.3;Mitotic rate in limb mesenchyme;480
1.51.4.2;Proximo-distal patterning of the limb skeleton;480
1.51.5;MESENCHYMAL FACTORS MAINTAIN THE AER;481
1.51.5.1;AEMF;481
1.51.5.2;The PNZ;481
1.51.6;SPECIFICITY OF LIMB-BUD EPITHELIUM;482
1.51.7;SPECIFICITY OF DISTAL LIMB MESENCHYME;484
1.51.8;THE TEMPORAL COMPONENT;485
1.51.9;A MECHANICAL ROLE FOR THE EPITHELIUM?;485
1.51.10;NOTES;486
1.52;Chapter 36 Adding or Deleting an AER;487
1.52.1;AER REGENERATION;487
1.52.2;EXPERIMENTAL REMOVAL OF THE AER;488
1.52.3;FAILURE TO MAINTAIN AN AER: WINGLESS (wl) MUTANTS;489
1.52.3.1;Mutual interaction;490
1.52.4;EXPERIMENTAL ADDITION OF AN AER;491
1.52.5;MUTANTS WITH DUPLICATED LIMBS;491
1.52.5.1;An enlarged AER;491
1.52.5.2;Duplicating the AER;493
1.52.5.3;Narrow or subdivided AERs;496
1.52.6;NOTES;496
1.53;Chapter 37 AERs in Limbed and Limbless Tetrapods;498
1.53.1;AERs ACROSS THE TETRAPODS;498
1.53.1.1;Amphibians;498
1.53.1.1.1;Anurans;498
1.53.1.1.2;Urodeles;499
1.53.1.2;Reptiles;499
1.53.1.3;Mammals;499
1.53.1.3.1;Mice;499
1.53.1.3.2;Chimaeras;500
1.53.1.3.3;Humans;501
1.53.2;LIMBLESS TETRAPODS;501
1.53.2.1;Evolutionary patterns;501
1.53.2.2;Gaining limbs back;501
1.53.2.3;Ecological correlates of limblessness;502
1.53.2.4;The developmental basis of limblessness in snakes and legless lizards;503
1.53.2.4.1;Inability to maintain an AER;504
1.53.2.4.2;Molecular mechanisms;505
1.53.3;NOTES;505
1.54;Part XIII Limbs and Limb Skeletons;508
1.55;Chapter 38 Axes and Polarity;510
1.55.1;ESTABLISHING AXES AND POLARITY;510
1.55.2;THE A-P AXIS AND THE ZPA;510
1.55.2.1;A role for Fgf-2;511
1.55.2.2;dHand and Shh;511
1.55.2.3;Wnts and Fgf;512
1.55.2.4;ZPAs abound;513
1.55.3;D-V POLARITY;513
1.55.4;P-D POLARITY AND THE PROGRESS ZONE;513
1.55.4.1;Extension to amphibian limb regeneration;513
1.55.5;CONNECTING D-V AND P-D POLARITY;514
1.55.6;THALIDOMIDE AND LIMB DEFECTS;514
1.55.6.1;Time of action;515
1.55.6.2;Mode of action;515
1.55.7;NOTES;517
1.56;Chapter 39 Patterning Limb Skeletons;519
1.56.1;MORPHOGENESIS AND GROWTH;519
1.56.2;PROGRAMMED CELL DEATH (APOPTOSIS);520
1.56.2.1;Posterior and anterior necrotic zones (PNZ, ANZ);520
1.56.2.2;Interdigital cell death;521
1.56.2.2.1;A role for BmpR-1;522
1.56.2.3;The opaque patch;523
1.56.3;CELL ADHESION AND MORPHOGENESIS: TALPID (ta) MUTANT FOWL;523
1.56.3.1;Talpid2;524
1.56.3.2;Talpid3;524
1.56.4;NOTES;526
1.57;Chapter 40 Before Limbs There Were Fins;527
1.57.1;DORSAL MEDIAN UNPAIRED FINS;527
1.57.1.1;Teleost fish;527
1.57.1.2;Life style;527
1.57.1.3;Developmental origins;528
1.57.1.4;Evolutionary origins;528
1.57.2;PAIRED FINS;532
1.57.2.1;Fin buds and fin folds;532
1.57.2.2;Fin skeletons;533
1.57.2.3;Retinoic acid;534
1.57.2.3.1;…Regeneration;535
1.57.2.3.2;An RA-Shh link;535
1.57.3;FIN REGENERATION;536
1.57.4;FINS . SUCKERS;536
1.57.5;FINS . LIMBS22;536
1.57.6;FROM MANY TO FEWER DIGITS;537
1.57.7;NOTES;538
1.58;Part XIV Backbones and Tails;540
1.59;Chapter 41 Vertebral Chondrogenesis: Spontaneous or Not?;542
1.59.1;SELF-DIFFERENTIATION OR INDUCTION?;542
1.59.2;MORPHOGENESIS;543
1.59.2.1;Spinal ganglia and vertebral morphogenesis;544
1.59.3;CHONDROGENESIS IN VITRO;545
1.59.4;SPONTANEOUS CHONDROGENESIS?;545
1.59.4.1;Environmental influences;546
1.59.4.2;Cell division and cell death;546
1.59.5;NOTES;547
1.60;Chapter 42 The Search for the Magic Bullet;548
1.60.1;INTEGRITY OF NOTOCHORD/SPINAL CORD AND VERTEBRAL MORPHOGENESIS;548
1.60.1.1;Fish skeletal defects;548
1.60.2;FOR HOW LONG ARE NOTOCHORD AND SPINAL CORD ACTIVE?;549
1.60.3;CAN DERMOMYOTOME OR LATERAL-PLATE MESODERM CHONDRIFY?;549
1.60.4;THE SEARCH FOR THE MAGIC BULLET;550
1.60.4.1;A role for ectoderm?;550
1.60.4.2;Cartilage cells as cartilage inducers;551
1.60.5;CHONDROCYTE EXTRACELLULAR MATRIX;552
1.60.6;NOTOCHORD AND SPINAL CORD EXTRACELLULAR MATRICES;552
1.60.7;GLYCOSAMINOGLYCANS;552
1.60.7.1;Collagens;553
1.60.8;FUNCTION OF NOTOCHORD AND SPINAL CORD MATRIX PRODUCTS;554
1.60.9;KEY ROLES FOR Pax-1 AND Pax-9;554
1.60.10;CONCLUSIONS;556
1.60.11;NOTES;556
1.61;Chapter 43 Tail Buds, Tails and Taillessness;558
1.61.1;EMBRYOLOGICAL ORIGIN;558
1.61.2;THE VENTRAL EPITHELIAL RIDGE (VER);558
1.61.3;Tbx GENES;560
1.61.4;TAIL GROWTH;560
1.61.4.1;Genes or environment;560
1.61.4.2;Temperature;560
1.61.5;TEMPERATURE-INDUCED CHANGE IN VERTEBRAL NUMBER: MERISTIC VARIATION;563
1.61.5.1;Natural variation and adaptive value;563
1.61.5.2;Studies with teleost fish;564
1.61.5.3;Studies with avian embryos;564
1.61.5.4;Studies with mammals;564
1.61.5.5;Studies with amphibian embryos;565
1.61.5.6;Temperature plus…;565
1.61.6;TAILLESSNESS;565
1.61.7;AND THEREBY HANGS A TAIL;566
1.61.7.1;Fish tails;566
1.61.8;LIZARDS’ TAILS: AUTOTOMY;566
1.61.9;NOTES;566
1.62;Part XV Evolutionary Skeletal Biology;568
1.63;Chapter 44 Evolutionary Experimentation Revisited;570
1.63.1;VARIATION;570
1.63.1.1;Variation of individual elements;570
1.63.1.2;Variation that tests a hypothesis;571
1.63.1.3;Pattern variation;572
1.63.2;ADAPTIVE VALUE;572
1.63.3;METAMORPHOSIS;573
1.63.4;MINIATURIZATION;573
1.63.5;HETEROCHRONY;576
1.63.5.1;Process heterochrony;576
1.63.5.2;Coupling and uncoupling dermal and endochondral ossification;576
1.63.5.3;Primates;577
1.63.6;NEOMORPHS;577
1.63.6.1;The preglossale of the common pigeon;577
1.63.6.2;Digits;578
1.63.6.3;Secondary jaw articulations;578
1.63.6.4;A Boid intramaxillary joint;579
1.63.6.5;Regenerated joints;579
1.63.6.6;Wishbones;579
1.63.6.7;Limb rudiments in whales;579
1.63.6.8;Turtle shells;580
1.63.6.8.1;Development;580
1.63.6.8.2;Evolutionary history;580
1.63.7;ATAVISMS;583
1.63.7.1;Limb skeletal elements in whales;584
1.63.7.2;Mammalian teeth;584
1.63.7.3;Teleosts and taxic atavisms;584
1.63.7.4;Late-developing bones in anurans;585
1.63.8;NEOMORPH OR ATAVISM?;585
1.63.9;NOTES;586
1.64;References;588
1.65;Index;766

Leseproben

Preface The skeleton has fascinated humankind ever since it was realized that, aside from one or several sets of genes, bare bones are our only bequest to posterity. But the skeleton is more than an articulated set of bones: its three-dimensional conformation establishes the basis of our physical appearance; its formation and rate of differentiation determine our shape and size at birth; its 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 the developmental or cell biologist, the skeleton provides an excellent model for studies of gene action, cell differentiation, morphogenesis, polarized growth, epithelial–mesenchymal interactions, programmed cell death, and the role of the extracellular matrix. The skeleton supplies the geneticist with a permanent record of the vicissitudes of its growth, whereby the phenotypic expression of genetic abnormalities can be studied. The orthopaedic surgeon earns a livelihood from correcting abnormalities and breaks, while the orthodontist corrects 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. Haematologists, on the other hand, 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 bones and small. Bones exhibit bumps, ridges, grooves, holes and depressions where they articulate with other bones, 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 benign soft tissues. Bones and cartilages may develop during embryonic or foetal 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. My previous book on the skeleton – Developmental and Cellular Skeletal Biology – was published in 1978. That book concerned itself with how bones and cartilages are made and how these tissues, organs and systems evolved. So too does the present book, which includes and updates the earlier treatment. With respect to skeletal development, I address such questions as the following. • Is bone always bone, no matter where and under what conditions it forms? • Do bones that develop indirectly by replacing another tissue – be it cartilage, marrow, connective tissue, fat, tendon or ligament – differ from one another, and/or from bone that develops directly (intramembranously)? • Is fast-growing the same as slow-growing bone? • Is fish bone the same as human bone? • Does bone form continuously or in cycles? • Do bears make new bone during hibernation? • Can sharks make bone? • If cartilage does not contain type II (cartilage-type) collagen, is it still cartilage? • Does the body contain cells that can differentiate as chondrocytes or as osteocytes and, if so, what factors allow cells to choose their fate? • Are progenitor (stem) cells for bone and cartilage only found within the skeleton? If not, how do we recognize such cells and activate them for skeletogenesis? • Why is aggregation (condensation) of cells so important for the initiation of the skeleton? • Does the skeleton display daily or circadian rhythms? • Do similar genes/growth factors regulate the differentiation of osteoblasts and chondroblasts? • Can mononucleated cells resorb bone? • How do joints form and remain patent? • How does activating FGF receptors cause cranial sutures to fuse? • What can mutants tell us about normal skeletogenesis? • Does Wolff’s law really govern the structure of bone? • How do chondroid, chondroid bone, osteoid and bone differ from one another? • How do antlers, horns and knobs (ossicones) differ one from the other? • Can we restart cell division in articular cartilage to effect repair? With respect to the evolution of skeletal tissues, organs and systems, I ask such questions as the following. • What are the evolutionary relationships between cartilage and bone and between acellular and cellular bone? • How did novel features such as tetrapod limbs arise from fish fins? • Can fossilized bone reveal patterns of growth, metabolism or physiology? • Why are so few aware of the extensive cartilaginous skeletons found in many invertebrates? • Is five the canonical number of tetrapod digits? • If tetrapods are vertebrates with limbs, then how can limbless snakes be tetrapods? • How did snakes lose their limbs? • How did whales lose their hind limbs and transform their forelimbs into flippers? • How do we recognize the diverse range of tissues in fossilized skeletons that are intermediate between connective tissues and cartilage, cartilage and bone, bone and dentine, or dentine and enamel? • Why can some vertebrates regenerate their limbs or tails and others not? • How does reduction in body size (miniaturization) affect the skeleton? The answers to the above and many other questions may be found in this book. Sometimes the ‘answers’ are limited to descriptions. In other cases we have an extensive knowledge of the molecular, cellular, developmental and evolutionary processes involved. Some transitions (fins ? limbs, for example) are understood in considerable detail, with paleontology, paleobiology, paleohistology, paleopathology, and the study of extant forms through molecular, cell and developmental biology contributing to our understanding. Other transitions – the origin of the turtle shell, for example – are much less well understood, with fossils contributing little and developmental information only beginning to appear. Discussion of the mechanisms of skeletal development and evolution is organized into 15 parts to enable you to select with ease a topic of special interest. The range of skeletal tissues covered by the book is outlined in Part I. Although primarily devoted to bone and cartilage, Part I introduces dentine and enamel and four skeletal tissues that I call ‘intermediate’ because they display features of two or more of cartilage, bone, dentine and enamel. The four are chondroid, chondroid bone, cementum and enameloid. Discussion of these intermediate tissues is expanded in Part II in the context of what I refer to as ‘natural experiments,’ a category that includes invertebrate cartilages and an examination of the evolution of skeletal tissues. Unusual tissues are followed in Part III by unusual modes of skeletogenesis, namely, horns, antlers, intratendinous ossifications and sesamoids, and the ossicones (knobs) of giraffes. Parts IV and V deal with the origin of skeletogenic cells, either as stem cells in embryos or adults (Chapters 10 and 11) or as more definitive skeletogenic cells (Part V). Here the emphasis is on those cells that can differentiate either as chondro- or osteoblasts (Chapter 12), on dedifferentiation as a source of skeletogenic cells in normally developing long bones and jaws and in regenerating urodele limbs (Chapters 13 and 14), and on the relationship(s) between the cells that make and the cells that break bone – osteoblasts and osteoclasts (Chapter 15). I move explicitly into embryonic development in the three chapters in Part VI through examination of the embryonic origins of skeletogenic cells in somitic mesoderm and the neural crest, and an evaluation of the roles of epithelial–mesenchymal interactions in initiating skeletogenesis. The developmental processes that underpin skeletal formation – differentiation, morphogenesis and growth – are mediated through modification of cell division, movement, death (apoptosis) and/or specialization. To our amazement, similar genes and gene networks or pathways may be...