Principles of development

Cover......Page 1
Summary of contents......Page 12
Contents......Page 14
List of boxes......Page 23
Reviewer acknowledgements......Page 25
1 History and basic concepts......Page 26
  1.1 Aristotle first defined the problem of epigenesis versus preformation......Page 28
  1.2 Cell theory changed how people thought about embryonic development and heredity......Page 29
  1.3 Two main types of development were originally proposed......Page 31
  BOX 1B The mitotic cell cycle......Page 32
  1.5 Developmental biology emerged from the coming together of genetics and embryology......Page 33
  1.6 Development is studied mainly through selected model organisms......Page 34
  1.7 The first developmental genes were identified as spontaneous mutations......Page 36
 A conceptual tool kit......Page 38
  1.8 Development involves the emergence of pattern, change in form, cell differentiation, and growth......Page 39
  BOX 1C Germ layers......Page 40
  1.10 Genes control cell behavior by specifying which proteins are made......Page 42
  1.11 The expression of developmental genes is under tight control......Page 44
  BOX 1D Visualizing gene expression in embryos......Page 45
  1.12 Development is progressive and the fates of cells become determined at different times......Page 47
  1.13 Inductive interactions make cells different from each other......Page 49
  1.14 The response to inductive signals depends on the state of the cell......Page 51
  1.15 Patterning can involve the interpretation of positional information......Page 52
  BOX 1F When development goes awry......Page 53
  1.17 Localization of cytoplasmic determinants and asymmetric cell division can make daughter cells different from each other......Page 55
  1.18 The embryo contains a generative rather than a descriptive program......Page 56
  1.20 The complexity of embryonic development is due to the complexity of cells themselves......Page 57
  1.21 Development is a central element in evolution......Page 58
 Summary to Chapter 1......Page 59
2 Development of theDrosophila body plan......Page 62
  2.1 The early Drosophila embryo is a multinucleate syncytium......Page 63
  2.2 Cellularization is followed by gastrulation and segmentation......Page 65
  2.4 Many developmental genes were identified in Drosophila through induced large-scale genetic screening......Page 66
  BOX 2A Mutagenesis and genetic screening strategy for identifying developmental mutants in Drosophila......Page 68
  2.5 The body axes are set up while the Drosophila embryo is still a syncytium......Page 69
  2.8 Bicoid protein provides an antero-posterior gradient of a morphogen......Page 71
  2.9 The posterior pattern is controlled by the gradients of Nanos and Caudal proteins......Page 74
  2.10 The anterior and posterior extremities of the embryo are specified by activation of a cell-surface receptor......Page 75
  2.11 The dorso-ventral polarity of the embryo is specified by localization of maternal proteins in the egg vitelline envelope......Page 76
  2.12 Positional information along the dorso-ventral axis is provided by the Dorsal protein......Page 77
  SUMMARY......Page 78
 Localization of maternal determinants during oogenesis......Page 79
  2.13 The antero-posterior axis of the Drosophila egg is specified by signals from the preceding egg chamber and by interactions of the oocyte with follicle cells......Page 80
  BOX 2C The JAK–STAT signaling pathway......Page 82
  2.14 Localization of maternal mRNAs to either end of the egg depends on the reorganization of the oocyte cytoskeleton......Page 83
  SUMMARY......Page 85
  2.16 The expression of zygotic genes along the dorso-ventral axis is controlled by Dorsal protein......Page 86
  2.17 The Decapentaplegic protein acts as a morphogen to pattern the dorsal region......Page 89
  2.19 Bicoid protein provides a positional signal for the anterior expression of zygotic hunchback......Page 91
  2.20 The gradient in Hunchback protein activates and represses other gap genes......Page 93
  BOX 2D P-element-mediated transformation......Page 94
  BOX 2E Targeted gene expression and misexpression screening......Page 95
 Activation of the pair-rule genes and the establishment of parasegments......Page 96
  2.22 Gap-gene activity positions stripes of pair-rule gene expression......Page 97
  2.23 Some insects use different mechanisms for patterning the body plan......Page 100
  2.24 Expression of the engrailed gene defines the boundary of a parasegment which is also a boundary of cell-lineage restriction......Page 102
  2.26 Signals generated at the parasegment boundary delimit and pattern the future segments......Page 104
  BOX 2F The Hedgehog signaling pathway......Page 107
  2.27 Compartment boundaries persist into the adult fly......Page 108
  BOX 2G Mutants in denticle pattern provided clues to the logic of segment patterning......Page 109
  BOX 2H Genetic mosaics and mitotic recombination......Page 111
  2.28 Insect epidermal cells become individually polarized in an antero-posteriordirection in the plane of the epithelium......Page 112
  BOX 2I Planar cell polarity in Drosophila......Page 113
  SUMMARY......Page 114
 Specification of segment identity......Page 115
  2.29 Segment identity in Drosophila is specified by Hox genes......Page 116
  2.30 Homeotic selector genes of the bithorax complex are responsible for diversification of the posterior segments......Page 117
  2.32 The order of Hox gene expression corresponds to the order of genes along the chromosome......Page 118
  SUMMARY......Page 119
 Summary to Chapter 2......Page 120
3 Vertebrate development I: life cycles and experimental techniques......Page 128
 Vertebrate life cycles and outlines of development......Page 129
  3.1 The frog Xenopus laevis is the model amphibian for studying development of the body plan......Page 132
  3.2 The zebrafish embryo develops around a large mass of yolk......Page 136
  3.3 Birds and mammals resemble each other and differ from Xenopus in some important features of early development......Page 138
  3.4 The early chicken embryo develops as a flat disc of cells overlying a massive yolk......Page 139
  3.5 The mouse egg has no yolk and early development involves the allocation of cells to form the placenta and extra-embryonic membranes......Page 144
  3.6 The early development of a human embryo is similar to that of the mouse......Page 148
 Experimental approaches to studying vertebrate development......Page 150
  BOX 3A Preimplantation genetic diagnosis......Page 151
  BOX 3B Gene-expression profiling by DNA microarrays and RNA seq......Page 153
  3.7 Fate mapping and lineage tracing reveal which parts of the body cells in the early embryo give rise to which adult structures......Page 154
  3.8 Not all techniques are equally applicable to all vertebrates......Page 156
  3.9 Developmental genes can be identified by spontaneous mutation and by large-scale mutagenesis screens......Page 157
  BOX 3C Large-scale mutagenesis screens for recessive mutations in zebrafish......Page 159
  3.10 Transgenic techniques enable animals to be produced with mutations in specific genes......Page 160
  BOX 3D The Cre/loxP system: a strategy for making gene knock-outs in mice......Page 163
  3.12 Gene regulatory networks in embryonic development can be revealed by chromatin immunoprecipitation techniques......Page 164
 Summary to Chapter 3......Page 165
4 Vertebrate development II: Xenopus and zebrafish......Page 169
  4.1 The animal–vegetal axis is maternally determined in Xenopus......Page 170
  BOX 4A Intercellular protein signals in vertebrate development......Page 172
  BOX 4B The Wnt/β-catenin signaling pathway......Page 173
  4.2 Local activation of Wnt/β-catenin signaling specifies the future dorsal side of the embryo......Page 174
  4.3 Signaling centers develop on the dorsal side of the blastula......Page 176
 The origin and specification of the germ layers......Page 177
  4.4 The fate map of the Xenopus blastula makes clear the function of gastrulation......Page 178
  4.6 Endoderm and ectoderm are specified by maternal factors, whereas mesoderm is induced from ectoderm by signals from the vegetal region......Page 179
  4.7 Mesoderm induction occurs during a limited period in the blastula stage......Page 182
  4.8 Zygotic gene expression is turned on at the mid-blastula transition......Page 183
  4.9 Mesoderm-inducing and patterning signals are produced by the vegetal region, the organizer, and the ventral mesoderm......Page 184
  4.10 Members of the TGF-β family have been identified as mesoderm inducers......Page 185
  4.11 The zygotic expression of mesoderm-inducing and patterning signals is activated by the combined actions of maternal VegT and Wnt signaling......Page 186
  4.12 Threshold responses to gradients of signaling proteins are likely to pattern the mesoderm......Page 187
 The Spemann organizer and neural induction......Page 189
  BOX 4E The FGF signaling pathway......Page 190
  4.13 Signals from the organizer pattern the mesoderm dorso-ventrally by antagonizing the effects of ventral signals......Page 191
  4.14 The antero-posterior axis of the embryo emerges during gastrulation......Page 192
  4.15 The neural plate is induced in the ectoderm......Page 194
  4.16 The nervous system is patterned along the antero-posterior axis by signals from the mesoderm......Page 197
  4.17 The final body plan emerges by the end of gastrulation and neurulation......Page 198
 Development of the body plan in zebrafish......Page 199
  4.19 The germ layers are specified in the zebrafish blastoderm by similar signals to those in Xenopus......Page 200
  4.20 The shield in zebrafish is the embryonic organizer like the Spemann organizer in Xenopus......Page 202
 Summary to Chapter 4......Page 203
5 Vertebrate development III: Chick and mouse—completing the body plan......Page 210
  5.1 The antero-posterior polarity of the chick blastoderm is related to the primitive streak......Page 211
  5.2 Early stages in mouse development establish separate cell lineages for the embryo and the extra-embryonic structures......Page 213
  5.3 Movement of the anterior visceral endoderm indicates the definitive antero-posterior axis in the mouse embryo......Page 217
  5.4 The fate maps of vertebrate embryos are variations on a basic plan......Page 218
  BOX 5A Fine-tuning Nodal signaling......Page 219
  5.5 Mesoderm induction and patterning in the chick and mouse occurs during primitive-streak formation......Page 221
  5.6 The node that develops at the anterior end of the streak in chick and mouse embryos is equivalent to the Spemann organizer in Xenopus......Page 223
  5.7 Neural induction in chick and mouse is initiated by FGF signaling with inhibition of BMP signaling being required in a later step......Page 225
  BOX 5B Chromatin-remodeling complexes......Page 227
  5.8 Axial structures in chick and mouse are generated from self-renewing cell populations......Page 228
  SUMMARY......Page 230
  BOX 5C Retinoic acid: a small-molecule intercellular signal......Page 231
 Somite formation and antero-posterior patterning......Page 232
  5.9 Somites are formed in a well-defined order along the antero-posterior axis......Page 233
  BOX 5D The Notch signaling pathway......Page 237
  5.10 Identity of somites along the antero-posterior axis is specified by Hox gene expression......Page 238
  BOX 5E The Hox genes......Page 240
  5.11 Deletion or overexpression of Hox genes causes changes in axial patterning......Page 243
  5.12 Hox gene expression is activated in an anterior to posterior pattern......Page 244
  5.13 The fate of somite cells is determined by signals from the adjacent tissues......Page 245
  SUMMARY......Page 247
  5.14 Neural crest cells arise from the borders of the neural plate and migrate to give rise to a wide range of different cell types......Page 248
  5.15 Neural crest cells migrate from the hindbrain to populate the branchial arches......Page 249
  SUMMARY......Page 250
  5.16 The bilateral symmetry of the early embryo is broken to produce left–right asymmetry of internal organs......Page 251
  5.17 Left–right symmetry breaking may be initiated within cells of the early embryo......Page 253
 Summary to Chapter 5......Page 254
6 Development of nematodes and sea urchins......Page 260
 Nematodes......Page 261
  BOX 6A Apoptotic pathways in nematodes, Drosophila and mammals......Page 263
  6.2 The antero-posterior axis in Caenorhabditis elegans is determined by asymmetric cell division......Page 264
  BOX 6B Gene silencing by antisense RNA and RNA interference......Page 266
  6.3 The dorso-ventral axis in Caenorhabditis elegans is determined by cell–cell interactions......Page 267
  6.4 Both asymmetric divisions and cell–cell interactions specify cell fate in the early nematode embryo......Page 269
  6.5 Cell differentiation in the nematode is closely linked to the pattern of cell division......Page 271
  6.6 Hox genes specify positional identity along the antero-posterior axis in Caenorhabditis elegans......Page 272
  6.7 The timing of events in nematode development is under genetic control that involves microRNAs......Page 273
  6.8 Vulval development is initiated by the induction of a small number of cells by short-range signals from a single inducing cell......Page 275
  SUMMARY......Page 278
  6.9 The sea-urchin embryo develops into a free-swimming larva......Page 279
  6.10 The sea-urchin egg is polarized along the animal–vegetal axis......Page 280
  6.11 The sea-urchin fate map is finely specified, yet considerable regulation is possible......Page 282
  6.12 The vegetal region of the sea-urchin embryo acts as an organizer......Page 283
  6.13 The sea-urchin vegetal region is demarcated by the nuclear accumulation of β-catenin......Page 284
  6.14 The animal–vegetal axis and the oral–aboral axis can be considered to correspond to the antero-posterior and dorso-ventral axes of other deuterostomes......Page 285
  6.15 The pluteus skeleton develops from the primary mesenchyme......Page 286
  6.16 The oral–aboral axis in sea urchins is related to the plane of the first cleavage......Page 288
  6.17 The oral ectoderm acts as an organizing region for the oral–aboral axis......Page 289
  BOX 6D The gene regulatory network for sea-urchin endomesoderm specification......Page 290
 Summary to Chapter 6......Page 291
7 Plant development......Page 297
 7.1 The model plant Arabidopsis thaliana has a short life cycle and a small diploid genome......Page 299
  7.2 Plant embryos develop through several distinct stages......Page 300
  BOX 7A Angiosperm embryogenesis......Page 301
  7.3 Gradients of the signal molecule auxin establish the embryonic apical–basal axis......Page 303
  7.4 Plant somatic cells can give rise to embryos and seedlings......Page 305
  7.5 Cell enlargement is a major process in plant growth and morphogenesis......Page 306
  SUMMARY......Page 307
 Meristems......Page 308
  7.7 The size of the stem-cell area in the meristem is kept constant by a feedback loop to the organizing center......Page 309
  7.8 The fate of cells from different meristem layers can be changed by changing their position......Page 310
  7.9 A fate map for the embryonic shoot meristem can be deduced using clonal analysis......Page 312
  7.10 Meristem development is dependent on signals from other parts of the plant......Page 313
  7.11 Gene activity patterns the proximo-distal and adaxial–abaxial axes of leaves developing from the shoot meristem......Page 314
  7.12 The regular arrangement of leaves on a stem is generated by regulated auxin transport......Page 315
  7.13 Root tissues are produced from Arabidopsis root apical meristems by a highly stereotyped pattern of cell divisions......Page 317
  SUMMARY......Page 319
 Flower development and control of flowering......Page 320
  7.15 Homeotic genes control organ identity in the flower......Page 321
  BOX 7C The basic model for the patterning of the Arabidopsis flower......Page 323
  7.16 The Antirrhinum flower is patterned dorso-ventrally as well as radially......Page 324
  7.18 The transition of a shoot meristem to a floral meristem is under environmental and genetic control......Page 325
  7.19 Most flowering plants are hermaphrodites, but some produce unisexual flowers......Page 327
  SUMMARY......Page 328
 Summary to Chapter 7......Page 329
8 Cell differentiation and stem cells......Page 334
 The control of gene expression......Page 337
  8.1 Control of transcription involves both general and tissue-specific transcriptional regulators......Page 338
  8.2 Gene expression is also controlled by chemical and structural modifications to DNA and histone proteins that alter chromatin structure......Page 341
  BOX 8A Epigenetic control of gene expression by chromatin modification......Page 342
  8.3 Patterns of gene activity can be inherited by persistence of gene-regulatoryproteins or by maintenance of chromatin modifications......Page 343
  8.4 Changes in patterns of gene activity during differentiation can be triggered by extracellular signals......Page 344
  SUMMARY......Page 346
  8.5 Muscle differentiation is determined by the MyoD family of transcription factors......Page 347
  8.6 The differentiation of muscle cells involves withdrawal from the cell cycle, but is reversible......Page 349
  8.7 All blood cells are derived from multipotent stem cells......Page 350
  8.8 Intrinsic and extrinsic changes control differentiation of the hematopoietic lineages......Page 353
  8.9 Developmentally regulated globin gene expression is controlled by regulatory sequences far distant from the coding regions......Page 355
  8.10 The epidermis of adult mammalian skin is continually being replaced by derivatives of stem cells......Page 357
  8.11 Stem cells use different modes of division to maintain tissues......Page 359
  8.12 The lining of the gut is another epithelial tissue that requires continuous renewal......Page 361
  8.13 Skeletal muscle and neural cells can be renewed from stem cells in adults......Page 363
  8.14 Embryonic stem cells can proliferate and differentiate into many cell types in culture and contribute to normal development in vivo......Page 364
  BOX 8B The derivation and culture of mouse embryonic stem cells (ES cells)......Page 366
  SUMMARY......Page 367
 The plasticity of the differentiated state......Page 368
  8.15 Nuclei of differentiated cells can support development......Page 369
  8.17 The differentiated state of a cell can change by transdifferentiation......Page 371
  8.18 Stem cells could be a key to regenerative medicine......Page 373
  BOX 8C Tissue engineering using stem cells......Page 374
  BOX 8D Induced pluripotent stem cells (iPS cells)......Page 375
  8.19 Various approaches can be used to generate differentiated cells for cell-replacementtherapies......Page 377
 Summary to Chapter 8......Page 380
9 Morphogenesis: change in form in the early embryo......Page 386
  9.1 Sorting out of dissociated cells demonstrates differences in cell adhesiveness in different tissues......Page 388
  BOX 9A Cell-adhesion molecules and cell junctions......Page 390
  9.2 Cadherins can provide adhesive specificity......Page 391
  9.3 Transitions of tissues from an epithelial to a mesenchymal state, and vice versa, involve changes in adhesive junctions......Page 392
  BOX 9B The cytoskeleton, cell-shape change and cell movement......Page 393
 Cleavage and formation of the blastula......Page 394
  9.4 The orientation of the mitotic spindle determines the plane of cleavage at cell division......Page 395
  9.5 The positioning of the spindle within the cell also determines whether daughter cells will be the same or different sizes......Page 397
  9.6 Cells become polarized in the sea-urchin blastula and the mouse morula......Page 398
  9.7 Fluid accumulation as a result of tight-junction formation and ion transport forms the blastocoel of the mammalian blastocyst......Page 400
  SUMMARY......Page 401
  9.8 Gastrulation in the sea urchin involves an epithelial-to-mesenchymal transition, cell migration, and invagination of the blastula wall......Page 402
  9.9 Mesoderm invagination in Drosophila is due to changes in cell shape controlled by genes that pattern the dorso-ventral axis......Page 405
  9.10 Germ-band extension in Drosophila involves myosin-dependent remodeling of cell junctions and cell intercalation......Page 407
  9.11 Gastrulation in amphibians and fish involves involution, epiboly, and convergent extension......Page 408
  BOX 9C Convergent extension......Page 410
  9.12 Xenopus notochord development illustrates the dependence of medio-lateralcell polarity on a pre-existing antero-posterior polarity......Page 412
  9.13 Gastrulation in chick and mouse embryos involves the delamination of cells from the epiblast and their ingression through the primitive streak......Page 414
  SUMMARY......Page 416
 Neural tube formation......Page 417
  9.14 Neural tube formation is driven by changes in cell shape and convergent extension......Page 418
  BOX 9D Eph receptors and their ephrin ligands......Page 420
  SUMMARY......Page 421
  9.16 Neural crest migration is controlled by environmental cues......Page 422
  9.17 The formation of the lateral-line primordium in fishes is an example of collective cell migration......Page 424
  9.18 Dorsal closure in Drosophila and ventral closure in Caenorhabditis elegans are brought about by the action of filopodia......Page 425
  SUMMARY......Page 426
  9.19 Later extension and stiffening of the notochord occurs by directed dilation......Page 427
  SUMMARY......Page 428
 Summary to Chapter 9......Page 429
10 Germ cells, fertilization, and sex......Page 434
 The development of germ cells......Page 435
  10.1 Germ-cell fate is specified in some embryos by a distinct germplasm in the egg......Page 436
  10.2 In mammals germ cells are induced by cell–cell interactions during development......Page 438
  10.3 Germ cells migrate from their site of origin to the gonad......Page 439
  10.4 Germ cells are guided to their final destination by chemical signals......Page 440
  10.5 Germ-cell differentiation involves a halving of chromosome number by meiosis......Page 441
  BOX 10A Polar bodies......Page 442
  10.6 Oocyte development can involve gene amplification and contributions from other cells......Page 444
  10.8 In mammals some genes controlling embryonic growth are ‘imprinted’......Page 445
  SUMMARY......Page 448
  10.9 Fertilization involves cell-surface interactions between egg and sperm......Page 449
  10.10 Changes in the egg plasma membrane and enveloping layers at fertilization block polyspermy......Page 451
  10.11 Sperm–egg fusion causes a calcium wave that results in egg activation......Page 452
  SUMMARY......Page 454
  10.12 The primary sex-determining gene in mammals is on the Y chromosome......Page 455
  10.13 Mammalian sexual phenotype is regulated by gonadal hormones......Page 456
  10.14 The primary sex-determining signal in Drosophila is the number of X chromosomes and is cell autonomous......Page 458
  10.15 Somatic sexual development in Caenorhabditis is determined by the number of X chromosomes......Page 460
  10.16 Determination of germ-cell sex depends on both genetic constitution and intercellular signals......Page 461
  10.17 Various strategies are used for dosage compensation of X-linked genes......Page 463
  SUMMARY......Page 465
 Summary to Chapter 10......Page 466
11 Organogenesis......Page 471
  11.1 The vertebrate limb develops from a limb bud......Page 472
  11.2 Genes expressed in the lateral plate mesoderm are involved in specifying the position and type of limb......Page 474
  11.3 The apical ectodermal ridge is required for limb outgrowth and the formation of structures along the proximo-distal axis of the limb......Page 476
  11.4 Outgrowth of the limb bud involves oriented cell behavior......Page 477
  11.6 How position along the proximo-distal axis of the limb bud is specified is still a matter of debate......Page 479
  11.7 The polarizing region specifies position along the limb’s antero-posterior axis......Page 481
  BOX 11A Teratogens and the consequences of damage to the developing embryo......Page 483
  BOX 11B Positional information and morphogen gradients......Page 485
  11.8 Sonic hedgehog is the polarizing region morphogen......Page 486
  11.9 How digit identity is encoded is not yet known......Page 487
  BOX 11C Too many fingers: mutations that affect antero-posterior patterning can cause polydactyly......Page 488
  11.10 The dorso-ventral axis of the limb is controlled by the ectoderm......Page 489
  11.11 Development of the limb is integrated by interactions between signaling centers......Page 490
  BOX 11D Sonic hedgehog signaling and the primary cilium......Page 491
  11.12 Different interpretations of the same positional signals give different limbs......Page 492
  11.13 Hox genes have multiple inputs into the patterning of the limbs......Page 493
  11.14 Self-organization may be involved in the development of the limb bud......Page 496
  BOX 11E Reaction–diffusion mechanisms......Page 497
  11.16 The initial development of cartilage, muscles, and tendons is autonomous......Page 498
  11.17 Joint formation involves secreted signals and mechanical stimuli......Page 499
  11.18 Separation of the digits is the result of programmed cell death......Page 500
 Insect wings and legs......Page 501
  11.19 The adult wing emerges at metamorphosis after folding and evagination of the wing imaginal disc......Page 502
  11.20 A signaling center at the boundary between anterior and posterior compartments patterns the Drosophila wing along the antero-posterior axis......Page 503
  11.22 Vestigial is a key regulator of wing development that acts to specify wing identity and control wing growt......Page 506
  11.24 The leg disc is patterned in a similar manner to the wing disc, except for the proximo-distal axis......Page 508
  11.25 Butterfly wing markings are organized by additional positional fields......Page 510
  11.26 Different imaginal discs can have the same positional values......Page 511
  SUMMARY......Page 513
 Vertebrate and insect eyes......Page 514
  11.27 The vertebrate eye develops mainly from the neural tube and the ectoderm of the head......Page 515
  11.28 Patterning of the Drosophila eye involves cell–cell interactions......Page 519
  SUMMARY......Page 522
 Vertebrate lungs and insect tracheal system......Page 523
  11.29 The vertebrate lung develops by branching of epithelial tubes......Page 524
  11.30 The Drosophila tracheal system is a prime example of branching morphogenesis......Page 525
  11.31 The vascular system develops by vasculogenesis followed by sprouting angiogenesis......Page 527
  11.32 The development of the vertebrate heart involves morphogenesis and patterning of a mesodermal tube......Page 529
  11.33 Tooth development involves epithelial–mesenchymal interactions and a homeobox gene code specifies tooth identity......Page 532
 Summary to Chapter 11......Page 535
12 Development of the nervous system......Page 545
  12.1 Initial regionalization of the vertebrate brain involves signals from local organizers......Page 547
  12.2 Local signaling centers pattern the brain along the antero-posterior axis......Page 548
  12.3 The cerebral cortex is patterned by signals from the anterior neural ridge......Page 549
  12.4 The hindbrain is segmented into rhombomeres by boundaries of cell-lineagerestriction......Page 550
  12.5 Hox genes provide positional information in the developing hindbrain......Page 552
  12.6 The pattern of differentiation of cells along the dorso-ventral axis of the spinal cord depends on ventral and dorsal signals......Page 553
  12.7 Neuronal subtypes in the ventral spinal cord are specified by the ventral to dorsal gradient of Shh......Page 555
  12.8 Spinal cord motor neurons at different dorso-ventral positions project to different trunk and limb muscles......Page 556
  12.9 Antero-posterior pattern in the spinal cord is determined in response to secreted signals from the node and adjacent mesoderm......Page 557
  12.10 Neurons in Drosophila arise from proneural clusters......Page 558
  12.11 The development of neurons in Drosophila involves asymmetric cell divisions and timed changes in gene expression......Page 561
  BOX 12A Specification of the sensory organs of adult Drosophila......Page 562
  12.12 The production of vertebrate neurons involves lateral inhibition, as in Drosophila......Page 563
  12.13 Neurons are formed in the proliferative zone of the vertebrate neural tube and migrate outwards......Page 564
  BOX 12B Timing the birth of cortical neurons......Page 566
  SUMMARY......Page 568
 Axon navigation......Page 569
  12.15 The growth cone controls the path taken by a growing axon......Page 570
  BOX 12C The development of the neural circuit for the knee-jerk reflex......Page 572
  12.16 Motor neuron axons in the chick limb are guided by ephrin–Eph interactions......Page 573
  12.17 Axons crossing the midline are both attracted and repelled......Page 574
  12.18 Neurons from the retina make ordered connections with visual centers in the brain......Page 575
  SUMMARY......Page 578
 Synapse formation and refinement......Page 579
  12.19 Synapse formation involves reciprocal interactions......Page 581
  BOX 12D Autism: a developmental disorder that involves synapse dysfunction......Page 583
  12.21 Neuronal cell death and survival involve both intrinsic and extrinsic factors......Page 584
  12.22 The map from eye to brain is refined by neural activity......Page 585
  SUMMARY......Page 586
 Summary to Chapter 12......Page 587
13 Growth, post-embryonic development and regeneration......Page 594
 Growth......Page 595
  13.1 Tissues can grow by cell proliferation, cell enlargement, or accretion......Page 596
  13.2 Cell proliferation is controlled by regulating entry into the cell cycle......Page 597
  13.3 Cell division in early development can be controlled by an intrinsic developmental program......Page 598
  13.4 Extrinsic signals coordinate cell division, cell growth, and cell death in the developing Drosophila wing......Page 599
  BOX 13A The core Hippo signaling pathways in Drosophila and mammals......Page 600
  13.5 Cancer can result from mutations in genes that control cell proliferation......Page 601
  13.6 Size-control mechanisms differ in different organs......Page 603
  13.7 Overall body size depends on the extent and the duration of growth......Page 605
  13.8 Hormones and growth factors coordinate the growth of different tissues and organs and contribute to determining overall body size......Page 606
  BOX 13B The major determinant of body size in dogs is the growth hormone–IGF-1 axis......Page 607
  13.9 Elongation of the long bones illustrates how growth can be determined by a combination of an intrinsic growth program and extracellular factors......Page 608
  BOX 13C Digit length ratio is determined in the embryo......Page 611
  13.10 The amount of nourishment an embryo receives can have profound effects in later life......Page 612
 Molting and metamorphosis......Page 613
  13.12 Insect body size is determined by the rate and duration of larval growth......Page 614
  13.13 Metamorphosis in amphibians is under hormonal control......Page 617
  SUMMARY......Page 618
 Regeneration......Page 619
  13.15 Regeneration of amphibian and insect limbs involves epimorphosis......Page 620
  BOX 13D Regeneration in Hydra......Page 621
  13.16 Amphibian