Chapter 1： History and Basic Concepts 3
The origins of developmental biology 3
1-1 Aristotle first defined the problem of epigenesis and preformation 3
Box 1A Basic stages of Xenopus laevis development 4
1-2 Cell theory changed the conception of embryonic development and heredity 5
1-3 Mosaic and regulative development 6
1-4 The discovery of induction 8
1-5 The coming together of genetics and development 8
A conceptual tool kit 9
1-6 Development involves cell division， the emergence of pattern，change in form，cell differentiation，and growth 9
Box 1 B Germ layers 11
1-7 Cell behavior provides the link between gene action and developmental processes 12
1-8 Genes control cell behavior by controlling which proteins are made by a cell 13
1-9 Differential gene activity controls development 14
1-10 Development is progressive and the fate of cells becomes determined at different times 15
1-11 Inductive interactions can make cells different from each other 17
1-12 The response to inductive signals depends on the state of the cell 18
1-13 Patterning can involve the interpretation of positional information 19
1-14 Lateral inhibition can generate spacing patterns 20
1-15 Localization of cytoplasmic determinants and asymmetric cell division can make cells different from each other 20
1-16 The embryo contains a generative rather than a descriptive program 21
Chapter 2：Model Systems 25
Model organisms：vertebrates 25
2-1 Amphibians：Xenopus laevis 26
Box 2A Polar body formation 27
2-2 Birds：the chicken 31
2-3 Mammals：the mouse 37
2-4 Fishes：the zebrafish 41
Model organisms：invertebrates 43
2-5 The fruit fly Drosophila melanogaster 43
2-6 The nematode Caenorhabditis elegans 47
Model systems：plants 49
2-7 Arabidopsis thaliana 50
Identifying developmental genes 52
2-8 Developmental genes can be identified by rare spontaneous mutation 53
2-9 Identification of developmental genes by induced mutation and screening 54
Box 2B Mutagenesis and genetic screening for identifying developmental mutants in Drosophila 56
Chapter 3： Patterning the Vertebrate Body PlanI： Axes and Germ Layers 63
Setting up the body axes 63
3-1 The animal-vegetal axis of Xenopus is maternally determined 63
Box 3A Protein intercellular signaling molecules 64
Box 3B In situ detection of gene expression 65
3-2 The dorso-ventral axis of amphibian embryos is determined by the site of sperm entry 66
3-3 The Nieuwkoop center is specified by cortical rotation 68
3-4 Maternal proteins with dorsalizing and ventralizing effects have been identified 69
3-5 The dorso-ventral axis of the chick blastoderm is specified in relation to the yolk and the ante ro-posterior axis is set by gravity 70
3-6 The axes of the mouse embryo are specified by cell—cell interactions 71
3-7 Specification of left-right handedness of internal organs requires special mechanisms 73
3-8 Organ handedness in vertebrates is under genetic control 73
The origin and specification of the germ layers 75
3-9 A fate map of the amphibian blastula is constructed by following the fate of labeled cells 75
3-10 The fate maps of vertebrates are variations on a basic plan 77
3-11 Cells of early vertebrate embryos do not yet have their fates determined 79
Box 3C Transgenic mice 81
3-12 In Xenopus the mesoderm is induced by signals from the vegetal region 81
3-13 The mesoderm is induced by a diffusible signal during a limited period of competence 83
3-14 An intrinsic timing mechanism controls the time of expression of mesoderm-specific genes 84
3-15 Several signals induce and pattern the mesoderm in the Xenopus blastula 85
3-16 Sources of the mesoderm-inducing signals 86
3-17 Candidate mesoderm inducers have been identified in Xenopus 87
3-18 Mesoderm patterning factors are produced within the mesoderm 88
3-19 Zygotic gene expression begins at the mid-blastula transition in Xenopus 90
3-20 Mesoderm induction activates genes that pattern the mesoderm 91
3-21 Gradients in protein signaling factors and threshold responses could pattern the mesoderm 92
Chapter 4： Patterning the Vertebrate Body PlanⅡ： The Mesoderm and Early Nervous System 98
Somite formation and patterning 98
4-1 Somites are formed in a well-defined order along the ante ro-posterior axis 99
4-2 The fate of somite cells is determined by signals from the adjacent tissues 100
4-3 Positional identity of somites along the antero-posterior axis is specified by Hox gene expression 102
Box 4A Homeobox genes 104
4-4 Deletion or overexpression of Hox genes causes changes in axial patterning 106
4-5 Retinoic acid can alter positional values 107
Box 4B Gene targeting： insertional mutagenesis and gene knock-out 108
The role of the organizer region and neural induction 110
4-6 The organizer can specify a new antero-posterior axis 110
4-7 The neural plate is induced by mesoderm 113
4-8 The nervous system can be patterned by signals from the mesoderm 114
4-9 Signals that pattern the neural plate may travel within the neural plate itself 116
4-10 The hindbrain is segmented into rhombomeres by boundaries of cell lineage restriction 117
4-11 Neural crest cells have positional values 119
4-12 Hox genes provide positional identity in the hindbrain region 119
4-13 The embryo is patterned by the neurula stage into organ-forming regions that can still regulate 121
Chapter 5： Development of the Drosophila Body Plan 127
Maternal genes set up the body axes 127
5-1 Three classes of maternal genes specify the ante ro-posterior axis 128
5-2 The bicoid gene provides an ante ro-posterior morphogen gradient 129
5-3 The posterior pattern is controlled by the gradients of nanos and caudal proteins 131
5-4 The anterior and posterior extremities of the embryo are specified by cell-surface receptor activation 132
5-5 The dorso-ventral polarity of the egg is specified by localization of maternal proteins in the vitelline envelope 133
5-6 Positional information along the dorso-ventral axis is provided by the dorsal protein 134
Polarization of the body axes during oogenesis 136
5-7 Antero-posterior and dorso-ventral axes of the oocyte are specified by interactions with follicle cells 136
Zygotic genes pattern the early embryo 139
5-8 The expression of zygotic genes along the dorso-ventral axis is controlled by dorsal protein 139
5-9 The decapentaplegic protein acts as a morphogen to pattern the dorsal region 141
5-10 The ante ro-posterior axis is divided up into broad regions by gap gene expression 142
5-11 bicoid protein provides a positional signal for the anterior expression of hunchback 143
Box 5A Transgenic flies 144
5-12 The gradient in hunchback protein activates and represses other gap genes 144
Segmentation： activation of the pair-rule genes 146
5-13 Parasegments are delimited by expression of pair-rule genes in a periodic pattern 146
5-14 Gap gene activity positions stripes of pair-rule gene expression 148
Segment polarity genes and compartments 150
5-15 Expression of the engrailed gene delimits a cell lineage boundary and defines a compartment 151
Box 5B Genetic mosaics and mitotic recombination 153
5-16 Segment polarity genes pattern the segments and stabilize parasegment and segment boundaries 155
5-17 Compartment boundaries are involved in patterning and polarizing segments 157
5-18 Some insects use different mechanisms for patterning the body plan 158
Segmentation： selector and homeotic genes 161
5-19 Homeotic selector genes of the bithorax complex are responsible for diversification of the posterior segments 162
5-20 The Antennapedia complex controls specification of anterior regions 164
5-21 The order of HOM gene expression corresponds to the order of genes along the chromosome 164
5-22 HOM gene expression in visceral mesoderm controls the structure of the adjacent gut 165
Chapter 6：Development of Invertebrates，Ascidians，and Slime Molds 173
Nematodes 173
6-1 The developmental axes are determined by asymmetric cell division and cell—cell interactions 173
6-2 Cell—cell interactions specify cell fate in the early nematode embryo 176
6-3 A small cluster of homeobox genes specify cell fate along the antero-posterior axis 177
6-4 Genes control graded temporal information in nematode development 178
Molluscs 180
6-5 The handedness of spiral cleavage is specified maternally 181
6-6 Body axes in molluscs are related to early cleavages 181
Annelids 183
6-7 The teloblasts are specified by localization of cytoplasmic factors 183
6-8 Antero-posterior patterning and segmentation in the leech is linked to a lineage mechanism 184
Echinoderms 186
6-9 The sea urchin egg is polarized along the animal-vegetal axis 187
6-10 The dorso-ventral axis in sea urchins is related to the plane of the first cleavage 188
6-11 The sea urchin fate map is very finely specified，yet considerable regulation is possible 189
6-12 The vegetal region of the sea urchin embryo acts as an organizer 190
6-13 The regulatory regions of sea urchin develop-mental genes are complex and modular 191
Ascidians 193
6-14 Muscle may be specified by localized cytoplasmic factors 193
6-15 Notochord development in ascidians requires induction 195
Cellular slime molds 196
6-16 Patterning of the slug involves cell sorting and positional signaling 197
6-17 Chemical signals direct cell differentiation in the slime mold 199
Chapter 7： Plant Development 204
Embryonic development 204
7-1 Electrical currents are involved in polarizing the Fucus zygote 205
7-2 Cell fate in early Fucus development is determined by the cell wall 206
7-3 Differences in cell size resulting from unequal divisions could specify cell type in the Volvox embryo 207
7-4 Both asymmetric cell divisions and cell position pattern the early embryos of flowering plants 208
Box 7A Angiosperm embryogenesis 209
7-5 The patterning of particular regions of the Arabidopsis embryo can be altered by mutation 210
7-6 Plant somatic cells can give rise to embryos and seedlings 211
Meristems 213
7-7 The fate of a cell in the shoot meristem is dependent on its position 214
7-8 Meristem development is dependent on signals from the plant 217
Box 7B Transgenic plants 218
7-9 Leaf positioning and phyllotaxy involves lateral inhibition 218
7-10 Root tissues are produced from root apical meristems by a highly stereotyped pattern of cell divisions 219
Flower development 221
7-11 Homeotic genes control organ identity in the flower 221
7-12 The transition to a floral meristem is under environmental and genetic control 226
7-13 The Antirrhinum flower is patterned dorso-ventrally as well as radially 226
7-14 The internal meristem layer can specify floral meristem patterning 227
Chapter 8： Morphogenesis： Change in Form in the Early Embryo 232
Cell adhesion 232
8-1 Sorting out of dissociated cells demonstrates differences in cell adhesiveness in different tissues 232
Box 8A Cell adhesion molecules 233
8-2 Cadherins can provide adhesive specificity 234
Cleavage and formation of the blastula 235
8-3 The asters of the mitotic apparatus determine the plane of cleavage at cell division 237
8-4 Cells become polarized in early mouse and sea urchin blastulas 238
8-5 Ion transport is involved in fluid accumulation in the blastocoel 240
8-6 Internal cavities can be created by cell death 241
Gastrulation 242
8-7 Gastrulation in the sea urchin involves cell migration and invagination 243
Box 8B Change in cell shape and cell movement 244
8-8 Mesoderm invagination in Drosophila is due to changes in cell shape，controlled by genes that pattern the dorso-ventral axis 246
8-9 Xenopus gastrulation involves several different types of tissue movement 247
8-10 Convergent extension and epiboly are due to cell intercalation 250
8-11 Notochord elongation is caused by cell intercalation 252
Neural tube formation 254
8-12 Neural tube formation is driven by both internal and external forces 254
8-13 Changes in the pattern of expression of cell adhesion molecules accompany neural tube formation 255
Cell migration 256
8-14 The directed migration of sea urchin primary mesenchyme cells is determined by the contacts of their filopodia to the blastocoel wall 257
8-15 Neural crest migration is controlled by environ-mental cues and adhesive differences 258
8-16 Slime mold aggregation involves chemotaxis and signal propagation 260
Directed dilation 262
8-17 Circumferential contraction of hypodermal cells elongates the nematode embryo 263
8-18 The direction of cell enlargement can determine the form of a plant leaf 263
Chapter 9： Cell Differentiation 271
The reversibility and inheritance of patterns of gene activity 271
9-1 Nuclei of differentiated cells can support develop-ment of the egg 272
9-2 Patterns of gene activity in differentiated cells can be changed by cell fusion 273
9-3 The differentiated state of a cell can change by transdifferentiation 274
9-4 Differentiation of cells that make antibodies is due to irreversible changes in their DNA 276
9-5 Maintenance and inheritance of patterns of gene activity may depend on regulatory proteins，as well as chemical and structural modifications of DNA 277
Control of specific gene expression 281
9-6 Control of transcription involves both general and tissue-specific transcriptional regulators 282
9-7 External signals can activate genes 284
Models of cell differentiation 287
9-8 A family of genes can activate muscle-specific transcription 287
9-9 The differentiation of muscle cells involves withdrawal from the cell cycle 288
9-10 Complex combinations of transcription factors control cell differentiation 289
9-11 All blood cells are derived from pluripotent stem cells 290
9-12 Colony-stimulating factors and intrinsic changes control differentiation of the hematopoietic lineages 291
9-13 Globin gene expression is controlled by distant upstream regulatory sequences 293
9-14 Neural crest cells differentiate into several cell types 295
9-15 Steroid hormones and polypeptide growth factors specify chromaffin cells and sympathetic neurons 297
9-16 Neural crest diversification involves signals for both specification of cell fate and selection for cell survival 297
9-17 Programmed cell death is under genetic control 298
Chapter 10：Organogenesis 304
The development of the chick limb 304
10-1 The vertebrate limb develops from a limb bud 305
10-2 Patterning of the limb involves positional information 305
10-3 The apical ectodermal ridge induces the progress zone 307
10-4 The polarizing region specifies position along the ante ro-posterior axis 308
10-5 Position along the proximo-distal axis may be specified by a timing mechanism 311
10-6 The dorso-ventral axis is controlled by the ectoderm 312
10-7 Different interpretations of the same positional signals give different limbs 312
10-8 Homeobox genes are involved in patterning the limbs and specifying their position 313
10-9 Self-organization may be involved in pattern formation in the limb bud 315
10-10 Limb muscle is patterned by the connective tissue 316
Box 10A Reaction-diffusion mechanisms 317
10-11 The initial development of cartilage， muscles，and tendons is autonomous 318
10-12 Separation of the digits is the result of programmed cell death 318
Insect imaginal discs 320
10-13 Signals from the ante ro-posterior compartment boundary pattern the wing imaginal disc 321
10-14 The dorso-ventral boundary of the wing acts as a pattern-organizing center 322
10-15 The leg disc is patterned in a similar manner to the wing disc，except for the proximo-distal axis 323
10-16 Butterfly wing markings are organized by additional positional fields 324
10-17 The segmental identity of imaginal discs is determined by the homeotic selector genes 325
The insect compound eye 328
10-18 Signals maintain progress of the morpho-genetic furrow and the ommatidia are spaced by lateral inhibition 329
10-19 The patterning of the cells in the ommatidium depends on intercellular interactions 329
10-20 The development of R7 depends on a signal from R8 330
10-21 Activation of the gene eyeless can initiate eye development 331
The nematode vulva 332
10-22 The anchor cell induces primary and secondary fates 333
Development of the kidney 334
10-23 The development of the ureteric bud and mesen-chymal tubules involves induction 334
Chapter 11： Development of the Nervous System 340
Specification of cell identity in the nervous system 340
11-1 Neurons in Drosophila arise from proneural clusters 340
11-2 Lateral inhibition allocates neuronal precursors 342
11-3 Asymmetric cell divisions are involved in Drosophila sensory organ development 343
11-4 The vertebrate nervous system is derived from the neural plate 344
11-5 Specification of vertebrate neuronal precursors involves lateral inhibition 345
11-6 The pattern of differentiation of cells along the dorso-ventral axis of the spinal cord depends on ventral and dorsal signals 346
11-7 Neurons in the mammalian central nervous system arise from asymmetric cell divisions，then migrate away from the proliferative zone 348
Axonalguidance 352
11-8 Motor neurons from the spinal cord make muscle-specific connections 353
11-9 The growth cone controls the path taken by the growing axon 354
11-10 Choice of axon pathway depends on environmental cues and neuronal identity 355
11-11 Neurons from the retina make ordered connections on the tectum to form a retino-tectal map 356
11-12 Axons may be guided by gradients of diffusible agents 358
Neuronal survival， synapse formation， and refinement 360
11-13 Many motor neurons die during limb innervation 361
11-14 Neuronal survival depends on competition for neurotrophic factors 361
11-15 Reciprocal interactions between nerve and muscle are involved in formation of the neuromuscular junction 362
11-16 The map from eye to brain is refined by neural activity 365
11-17 The ability of mature vertebrate axons to regenerate is restricted to peripheral nerves 367
Chapter 12：Germ Cells and Sex 372
Determination of the sexual phenotype 372
12-1 The primary sex-determining gene in mammals is on the Y chromosome 372
12-2 Mammalian sexual phenotype is regulated by gonadal hormones 373
12-3 In Drosophila， the primary sex-determining signal is the number of X chromosomes and is cell autonomous 374
12-4 Somatic sexual development in Caenorhabditis is determined by the number of X chromosomes 376
12-5 Most flowering plants are hermaphrodites，but some produce unisexual flowers 377
12-6 Germ cell sex determination may depend both on cell signals and genetic constitution 378
12-7 Various strategies are used for dosage compen-sation of X-linked genes 379
The development of germ cells 382
12-8 Germ cell fate can be specified by a distinct germ plasm in the egg 382
12-9 Pole plasm becomes localized at the posterior end of the Drosophila egg 384
12-10 Germ cells migrate from their site of origin to the gonad 384
12-11 Germ cell differentiation involves a reduction in chromosome number 385
12-12 Oocyte development can involve gene amplifi-cation and contributions from other cells 387
12-13 Genes controlling embryonic growth are imprinted 387
Fertilization 390
12-14 Fertilization involves cell-surface interactions between egg and sperm 391
12-15 Changes in the egg membrane at fertilization block polyspermy 392
12-16 A calcium wave initiated at fertilization results in egg activation 393
Chapter 13：Regeneration 401
Morphallaxis 401
13-1 Hydra grows continuously， with loss of cells from its ends and by budding 401
13-2 Regeneration in Hydra is polarized and does not depend on growth 402
13-3 The head region of Hydra acts both as an organizing region and as an inhibitor of inappropriate head formation 402
13-4 Head regeneration in Hydra can be accounted for in terms of two gradients 403
Epimorphosis 405
13-5 Vertebrate limb regeneration involves cell dedifferentiation and growth 406
13-6 The limb blastema gives rise to structures with positional values distal to the site of amputation 408
13-7 Retinoic acid can change proximo-distal positional values in regenerating limbs 410
13-8 Insect limbs intercalate positional values by both proximo-distal and circumferential growth 412
13-9 Polarized regeneration in plants is due to the polarized transport of auxin 413
Chapter 14： Growth and Post-Embryonic Development 418
Growth 418
14-1 Tissues can grow by cell proliferation，cell enlargement，or accretion 418
14-2 Cell proliferation can be controlled by an intrinsic program and by external signals 419
14-3 Growth of mammals is dependent on growth hormones 421
14-4 Developing organs can have their own intrinsic growth programs 423
14-5 Growth of the long bones occurs in the growth plates 424
14-6 Growth of vertebrate striated muscle is dependent on tension 426
14-7 The epithelia of adult mammalian skin and gut are continually replaced by derivatives of stem cells 426
14-8 Cancer can result from mutations in genes controlling cell multiplication and differentiation 430
14-9 Hormones control many features of plant growth 430
14-10 Cell enlargement is central to plant growth 431
Molting and metamorphosis 432
14-11 Arthropods have to molt in order to grow 433
14-12 Metamorphosis is under environmental and hormonal control 434
Aging and senescence 437
14-13 Genes can alter the timing of senescence 438
14-14 Cells senesce in culture 439
Chapter 15： Evolution and Development 444
Modification of development in evolution 444
15-1 Embryonic structures have acquired new functions during evolution 445
15-2 Limbs evolved from fins 446
15-3 Development of vertebrate and insect wings makes use of evolutionarily conserved mechanisms 449
15-4 Hox gene complexes have evolved through gene duplication 450
15-5 Changes in specification and interpretation of positional identity have generated the elaboration of vertebrate and arthropod body plans 451
15-6 The position and number of paired appendages in insects is dependent on Hox gene expression 453
15-7 The body plan of arthropods and vertebrates is similar，but the dorso-ventral axis is inverted 454
Changes in the timing of developmental processes during evolution 456
15-8 Changes in relative growth rates can alter the shapes of organisms 456
15-9 Evolution of life histories has implications for development 457
15-10 The timing of developmental events has changed during evolution 458