About the companion website, xi

Section 1: Groundwork, 1

1 The excitement of developmental biology, 3

Where the subject came from, 3

Impact of developmental biology, 4

Future impact, 5

2 How development works, 7

Ultrashort summary, 7

Gametogenesis, 10

Early development, 13

Growth and death, 19

3 Approaches to development: developmental genetics, 25

Developmental mutants, 25

Sex chromosomes, 27

Maternal and zygotic, 27

Genetic pathways, 28

Genetic mosaics, 30

Screening for mutants, 31

Cloning of genes, 32

Gain-and loss-of-function experiments, 32

Transgenesis, 32

Other gain-of- function techniques, 34

Targeted mutagenesis, 34

Other loss-of- function systems, 35

Gene duplication, 36

Limitations of developmental genetics, 37

4 Approaches to development: experimental embryology and its molecular basis, 39

Normal development, 39

Developmental commitment, 42

Criteria for proof, 48

Transcription factors, 48

Transcription factor families, 50

Other controls of gene activity, 51

Signaling systems, 51

Genetic regulatory networks, 57

5 Approaches to development: cell and molecular biology techniques, 61

Microscopy, 61

Optical techniques, 61

Confocal, multi-photon, and light sheet microscopes, 63

Image capture, 63

Anatomical and histological methods, 64

Microinjection, 66

Study of gene expression by molecular biology methods, 67

Study of gene expression by in situ methods, 72

Reporter genes, 75

Cell-labeling methods, 76

6 Cells into tissues, 81

Cells in embryos, 81

Cytoskeleton, 82

Small GTP-binding proteins, 84

Extracellular matrix, 84

Cell movement, 85

Epithelial organization, 86

Morphogenetic processes, 88

Section 2: Major model organisms, 97

7 Major model organisms, 99

The big six, 99

Access and micromanipulation, 101

Genetics and genomes, 101

Relevance and tempo, 102

Other organisms, 102

8 Xenopus, 107

Oogenesis, maturation, and fertilization, 108

Normal development, 109

Fate maps, 114

Experimental methods, 115

Processes of regional specification, 119

9 The zebrafish, 135

Normal development, 135

Fate map, 140

Genetics, 141

Reverse genetic methods, 144

Embryological techniques, 145

Regional specification, 145

Other roles of the zebrafish, 150

10 The chick, 153

Normal development, 154

Fate map, 158

Regional specification of the early embryo, 159

Description of organogenesis in the chick, 164

11 The mouse, 173

Mammalian fertilization, 173

Normal development of the mouse, 177

Fate map, 184

Regional specification in the mouse embryo, 185

Transgenic mice, 190

Embryonic stem cells, 192

Knockouts and knock-ins, 192

Nuclear transplantation and imprinting, 196

X-inactivation, 196

Teratocarcinoma, 198

12 Human early development, 203

Human reproduction, 203

Preimplantation development, 205

Human embryonic stem cells, 207

Human postimplantation development, 208

Postimplantation diagnosis: chorionic villus sampling and amniocentesis, 211

Ethics of human development, 211

13 Drosophila, 217

Insects, 217

Normal development, 219

Fate map, 222

Pole plasm, 224

Drosophila developmental genetics, 224

The developmental program, 227

The dorsoventral pattern, 228

The anteroposterior system, 232

14 Caenorhabditis elegans, 247

Adult anatomy, 248

Embryonic development, 249

Regional specification in the embryo, 251

Analysis of postembryonic development, 259

The germ line, 262

Programmed cell death, 264

Section 3: Organogenesis, 269

15 Techniques for studying organogenesis and postnatal development, 271

Genetics, 271

Clonal analysis, 275

Tissue and organ culture, 278

Cell analysis and separation, 279

16 Development of the nervous system, 283

Overall structure and cell types, 283

Regional specification, 286

Neurogenesis and gliogenesis, 292

The neural crest, 299

Development of neuronal connectivity, 303

17 Development of mesodermal organs, 315

Somitogenesis, 315

Myogenesis, 322

The kidney, 323

Germ cell and gonadal development, 326

Sex determination, 330

Limb development, 330

Blood and blood vessels, 340

The heart, 343

18 Development of endodermal organs, 355

Normal development, 355

Organization of the gut tube, 356

Fate map of the endoderm, 359

Experimental analysis of endoderm development, 359

The pancreas, 366

19 Drosophila imaginal discs, 373

Metamorphosis, 373

Genetic study of larval development, 374

Disc development, 378

Compartments and selector genes, 378

Regional patterning of the wing disc, 381

Regeneration and transdetermination, 384

Morphogen gradients and polarity, 387

Section 4: Growth, evolution, regeneration, 391

20 Tissue organization and stem cells, 393

Types of tissue, 393

Tissue renewal, 397

Stem cells, 401

Intestinal epithelium, 403

Epidermis, 408

Hair follicles, 410

Hematopoietic system, 415

Mesenchymal stem cells and “transdifferentiation”, 419

Spermatogonia, 419

21 Growth, aging, and cancer, 425

Growth: control of size and proportion, 425

Biochemical pathways of growth control, 426

Growth control in insects, 429

Growth control in mammals, 431

Liver regeneration, 433

Growth in stature, 434

Aging, 436

Cell autonomous processes, 437

The insulin pathway and aging, 438

Caloric restriction, 438

Cancer, 440

Classification of tumors and precursor lesions, 440

Molecular biology of cancer, 442

Cancer stem cells, 443

Cancer progression, 444

Cancer therapy, 445

22 Pluripotent stem cells and their applications, 449

Human embryonic stem cells, 449

Induced pluripotent stem cells, 451

Somatic cell nuclear transfer, 453

Direct reprogramming, 454

Applications of human pluripotent stem cells, 455

Cell transplantation therapy, 457

Cell transplantation therapies using pluripotent stem cells, 459

Transplantation therapy for diabetes, 460

Retinal pigment epithelium, 462

Spinal repair, 463

Cardiomyocytes, 463

Parkinson’s disease, 463

Introduction of new therapies, 465

23 Evolution and development, 469

Macroevolution, 470

Molecular taxonomy, 471

Phylogeny of animals, 472

The fossil record, 473

The primordial animal, 474

Basal animals, 479

What really happened in evolution?, 481

Segmented body plans and Hox genes, 482

Insect wings and legs, 483

Atavisms, 483

Vertebrate limbs, 485

24 Regeneration of missing parts, 491

Types of regeneration, 491

Distribution of regenerative capacity, 491

Planarian regeneration, 492

Insect limb regeneration, 497

Vertebrate limb regeneration, 499

The process of limb regeneration, 499

The source of cells for regeneration, 501

Regeneration of regional pattern, 502

Regeneration: ancestral or adaptive property?, 508

General properties of regeneration, 509

Glossary, 513

Index, 527