Principles of Development

Cover
Preface
Learning from this book
About the authors
Summary of contents
Contents
List of Boxes
1 History and basic concepts
	The origins of developmental biology
		1.1 Aristotle first defined the problem of epigenesis versus preformation
		Box 1A Basic stages of Xenopus laevis development
		1.2 Cell theory changed how people thought about embryonic development and heredity
		1.3 Two main types of development were originally proposed
		1.4 The discovery of induction showed that one group of cells could determine the development of neighboring cells
		1.5 Developmental biology emerged from the coming together of genetics and embryology
		1.6 Development is studied mainly through selected model organisms
		1.7 The first developmental genes were identified as spontaneous mutations
		Summary
	A conceptual tool kit
		1.8 Development involves the emergence of pattern, change in form, cell differentiation, and growth
		1.9 Cell behavior provides the link between gene action and developmental processes
		1.10 Genes control cell behavior by specifying which proteins are made
		1.11 The expression of developmental genes is under tight control
		Experimental Box 1D Visualizing gene expression in embryos
		1.12 Development is progressive and the fates of cells become determined at different times
		1.13 Inductive interactions make cells different from each other
		1.14 The response to inductive signals depends on the state of the cell
		1.15 Patterning can involve the interpretation of positional information
		Medical Box 1F When development goes awry
		1.16 Lateral inhibition can generate spacing patterns
		1.17 Localization of cytoplasmic determinants and asymmetric cell division can make daughter cells different from each other
		1.18 The embryo contains a generative rather than a descriptive program
		1.19 The reliability of development is achieved by various means
		1.20 The complexity of embryonic development is due to the complexity of cells themselves
		1.21 Development is a central element in evolution
		Summary
		Summary to Chapter 1
2 Development of the Drosophila body plan
	Drosophila life cycle and overall development
		2.1 The early Drosophila embryo is a multinucleate syncytium
		2.2 Cellularization is followed by gastrulation and segmentation
		2.3 After hatching, the Drosophila larva develops through several larval stages, pupates, and then undergoes metamorphosis to become an adult
		2.4 Many developmental genes were identified in Drosophila through large-scale genetic screening for induced mutations
		Experimental Box 2A Mutagenesis and genetic screening strategy for identifying developmental mutants in Drosophila
		Summary
	Setting up the body axes
		2.5 The body axes are set up while the Drosophila embryo is still a syncytium
		2.6 Maternal factors set up the body axes and direct the early stage of Drosophila development
		2.7 Three classes of maternal genes specify the antero-posterior axis
		2.8 Bicoid protein provides an antero-posterior gradient of a morphogen
		2.9 The posterior pattern is controlled by the gradients of Nanos and Caudal proteins
		2.10 The anterior and posterior extremities of the embryo are specified by activation of a cell-surface receptor
		2.11 The dorso-ventral polarity of the embryo is specified by localization of maternal proteins in the egg vitelline envelope
		2.12 Positional information along the dorso-ventral axis is provided by the Dorsal protein
		Summary
	Localization of maternal determinants during oogenesis
		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
		2.14 Localization of maternal mRNAs to either end of the egg depends on the reorganization of the oocyte cytoskeleton
		2.15 The dorso-ventral axis of the egg is specified by movement of the oocyte nucleus followed by signaling between oocyte and follicle cells
		Summary
	Patterning the early embryo
		2.16 The expression of zygotic genes along the dorso-ventral axis is controlled by Dorsal protein
		2.17 The Decapentaplegic protein acts as a morphogen to pattern the dorsal region
		2.18 The antero-posterior axis is divided up into broad regions by gap gene expression
		2.19 Bicoid protein provides a positional signal for the anterior expression of zygotic hunchback
		2.20 The gradient in Hunchback protein activates and represses other gap genes
		Experimental Box 2D Targeted gene expression and misexpression screening
		Summary
	Activation of the pair-rule genes and the establishment of parasegments
		2.21 Parasegments are delimited by expression of pair-rule genes in a periodic pattern
		2.22 Gap gene activity positions stripes of pair-rule gene expression
		Summary
	Segmentation genes and segment patterning
		2.23 Expression of the engrailed gene defines the boundary of a parasegment, which is also a boundary of cell lineage restriction
		2.24 Segmentation genes stabilize parasegment boundaries
		2.25 Signals generated at the parasegment boundary delimit and pattern the future segments
		Experimental Box 2F Mutants in denticle pattern provided clues to the logic of segment patterning
		Summary
	Specification of segment identity
		2.26 Segment identity in Drosophila is specified by Hox genes
		2.27 Homeotic selector genes of the bithorax complex are responsible for diversification of the posterior segments
		2.28 The Antennapedia complex controls specification of anterior regions
		2.29 The order of Hox gene expression corresponds to the order of genes along the chromosome
		2.30 The Drosophila head region is specified by genes other than the Hox genes
		Summary
		Summary to Chapter 2
3 Vertebrate development I: life cycles and experimental techniques
	Vertebrate life cycles and outlines of development
		3.1 The frog Xenopus laevis is the model amphibian for studying development of the body plan
		3.2 The zebrafish embryo develops around a large mass of yolk
		3.3 Birds and mammals resemble each other and differ from Xenopus in some important features of early development
		3.4 The early chicken embryo develops as a flat disc of cells overlying a massive yolk
		3.5 The mouse egg has no yolk and early development involves the allocation of cells to form the placenta and extra-embryonic membranes
	Experimental approaches to studying vertebrate development
		3.6 Gene expression in embryos can be mapped by in situ nucleic acid hybridization
		Experimental Box 3A Gene-expression profiling by DNA microarrays and RNA seq
		3.7 Fate mapping and lineage tracing reveal which cells in which parts of the early embryo give rise to particular adult structures
		3.8 Not all techniques are equally applicable to all vertebrates
		3.9 Developmental genes can be identified by spontaneous mutation and by large-scale mutagenesis screens
		Experimental Box 3B Large-scale mutagenesis screens for recessive mutations in zebrafish
		3.10 Transgenic techniques enable animals to be produced with mutations in specific genes
		Experimental Box 3C The Cre/loxP system: a strategy for making gene knock-outs in mice
		Experimental Box 3D The CRISPR-Cas9 genome-editing system
		3.11 Gene function can also be tested by transient transgenesis and gene silencing
	Human embryonic development
		3.12 The early development of a human embryo is similar to that of the mouse
		Medical Box 3E Preimplantation genetic diagnosis
		3.13 The timing of formation and the anatomy of the human placenta differs from that in the mouse
		3.14 Some studies of human development are possible but are subject to strict laws
		Box 3F Identical twins
		Summary to Chapter 3
4 Vertebrate development II: Xenopus and zebrafish
	Setting up the body axes
		4.1 The animal–vegetal axis is maternally determined in Xenopus
		4.2 Local activation of Wnt/β-catenin signaling specifies the future dorsal side of the embryo
		4.3 Signaling centers develop on the dorsal side of the blastula
	The origin and specification of the germ layers
		Summary
		4.4 The fate map of the Xenopus blastula makes clear the function of gastrulation
		4.5 Cells of the early Xenopus embryo do not yet have their fates determined and regulation is possible
		4.6 Endoderm and ectoderm are specified by maternal factors, whereas mesoderm is induced from ectoderm by signals from the vegetal region
		4.7 Mesoderm induction occurs during a limited period in the blastula stage
		4.8 Zygotic gene expression is turned on at the mid-blastula transition
		4.9 Mesoderm-inducing and patterning signals are produced by the vegetal region, the organizer, and the ventral mesoderm
		4.10 Members of the TGF-β family have been identified as mesoderm inducers
		4.11 The zygotic expression of mesoderm-inducing and patterning signals is activated by the combined actions of maternal VegT and Wnt signaling
		Experimental Box 4D Investigating receptor function using dominant-negative proteins
		4.12 Threshold responses to gradients of signaling proteins are likely to pattern the mesoderm
		Summary
	The Spemann organizer and neural induction
		4.13 Signals from the organizer pattern the mesoderm dorso-ventrally by antagonizing the effects of ventral signals
		4.14 The antero-posterior axis of the embryo emerges during gastrulation
		4.15 The neural plate is induced in the ectoderm
		4.16 The nervous system is patterned along the antero-posterior axis by signals from the mesoderm
		4.17 The final body plan emerges by the end of gastrulation and neurulation
	Development of the body plan in zebrafish
		Summary
		4.18 The body axes in zebrafish are established by maternal determinants
		4.19 The germ layers are specified in the zebrafish blastoderm by similar signals to those in Xenopus
		Box 4F A zebrafish gene regulatory network
		4.20 The shield in zebrafish is the embryonic organizer
		Summary to Chapter 4
5 Vertebrate development III: chick and mouse—completing the body plan
	Development of the body plan in chick and mouse and ­generation of the spinal cord
		5.1 The antero-posterior polarity of the chick blastoderm is related to the primitive streak
		5.2 Early stages in mouse development establish separate cell lineages for the embryo and the extra-embryonic structures
		5.3 Movement of the anterior visceral endoderm indicates the definitive antero-posterior axis in the mouse embryo
		5.4 The fate maps of vertebrate embryos are variations on a basic plan
		5.5 Mesoderm induction and patterning in the chick and mouse occurs during primitive streak formation
		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
		5.7 Neural induction in chick and mouse is initiated by FGF signaling with inhibition of BMP signaling being required in a later step
		5.8 Axial structures in chick and mouse are generated from self-renewing cell populations
		Summary
	Somite formation and antero-posterior patterning
		5.9 Somites are formed in a well-defined order along the antero-posterior axis
		5.10 Identity of somites along the antero-posterior axis is specified by Hox gene expression
		Box 5E The Hox genes
		5.11 Deletion or overexpression of Hox genes causes changes in axial patterning
		5.12 Hox gene expression is activated in an anterior to posterior pattern
		5.13 The fate of somite cells is determined by signals from the adjacent tissues
		Summary
	The origin and patterning of neural crest
		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
		5.15 Neural crest cells migrate from the hindbrain to populate the branchial arches
		Summary
	Determination of left–right asymmetry
		5.16 The bilateral symmetry of the early embryo is broken to produce left–right asymmetry of internal organs
		5.17 Left–right symmetry breaking may be initiated within cells of the early embryo
		Summary
		Summary to Chapter 5
6 Development of nematodes and sea urchins
	Nematodes
		6.1 The cell lineage of Caenorhabditis elegans is largely invariant
		6.2 The antero-posterior axis in Caenorhabditis elegans is determined by asymmetric cell division
		Experimental Box 6B Gene silencing by antisense RNA and RNA interference
		6.3 The dorso-ventral axis in Caenorhabditis elegans is determined by cell–cell interactions
		6.4 Both asymmetric divisions and cell–cell interactions specify cell fate in the early nematode embryo
		6.5 Cell differentiation in the nematode is closely linked to the pattern of cell division
		6.6 Hox genes specify positional identity along the antero-posterior axis in Caenorhabditis elegans
		6.7 The timing of events in nematode development is under genetic control that involves microRNAs
		Box 6C Gene silencing by microRNAs
		6.8 Vulval development is initiated through the induction of a small number of cells by short-range signals from a single inducing cell
		Summary
	Echinoderms
		6.9 The sea urchin embryo develops into a free-swimming larva
		6.10 The sea urchin egg is polarized along the animal–vegetal axis
		6.11 The sea urchin fate map is finely specified, yet considerable regulation is possible
		6.12 The vegetal region of the sea urchin embryo acts as an organizer
		6.13 The sea urchin vegetal region is demarcated by the nuclear accumulation of β-catenin
		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
		6.15 The pluteus skeleton develops from the primary mesenchyme
		6.16 The oral–aboral axis in sea urchins is related to the plane of the first cleavage
		6.17 The oral ectoderm acts as an organizing region for the oral–aboral axis
		Experimental Box 6D The gene regulatory network for sea urchin endomesoderm specification
		Summary
		Summary to Chapter 6
7 Morphogenesis: change in form in the early embryo
	Cell adhesion
		7.1 Sorting out of dissociated cells demonstrates differences in cell adhesiveness in different tissues
		7.2 Cadherins can provide adhesive specificity
		7.3 The activity of the cytoskeleton regulates the mechanical properties of cells and their interactions with each other
		7.4 Transitions of tissues from an epithelial to a mesenchymal state, and vice versa, involve changes in adhesive junctions
		Summary
	Cleavage and formation of the blastula
		7.5 The orientation of the mitotic spindle determines the plane of cleavage at cell division
		7.6 The positioning of the spindle within the cell also determines whether daughter cells will be the same or different sizes
		7.7 Cells become polarized in the sea urchin blastula and the mouse morula
		7.8 Fluid accumulation as a result of tight-junction formation and ion transport forms the blastocoel of the mammalian blastocyst
		Summary
	Gastrulation movements
		7.9 Gastrulation in the sea urchin involves an epithelial-to-mesenchymal transition, cell migration, and invagination of the blastula wall
		7.10 Mesoderm invagination in Drosophila is due to changes in cell shape controlled by genes that pattern the dorso-ventral axis
		7.11 Germ-band extension in Drosophila involves myosin-dependent remodeling of cell junctions and cell intercalation
		7.12 Planar cell polarity confers directionality on a tissue
		7.13 Gastrulation in amphibians and fish involves involution, epiboly, and convergent extension
		Box 7C Convergent extension
		7.14 Xenopus notochord development illustrates the dependence of medio-lateral cell elongation and cell intercalation on a pre-existing antero-posterior polarity
		7.15 Gastrulation in chick and mouse embryos involves the separation of individual cells from the epiblast and their ingression through the primitive streak
		Summary
	Neural tube formation
		7.16 Neural tube formation is driven by changes in cell shape and convergent extension
		Medical Box 7E Neural tube defects
		Summary
	Formation of tubes and branching morphogenesis
		7.17 The Drosophila tracheal system is a prime example of branching morphogenesis
		7.18 The vertebrate vascular system develops by vasculogenesis followed by sprouting angiogenesis
		7.19 New blood vessels are formed from pre-existing vessels in angiogenesis
		Summary
	Cell migration
		7.20 Embryonic neural crest gives rise to a wide range of different cell types
		7.21 Neural crest migration is controlled by environmental cues
		7.22 The formation of the lateral-line primordium in fishes is an example of collective cell migration
		7.23 Body wall closure occurs in Drosophila, Caenorhabditis, mammals, and chick
		Summary
		Summary to Chapter 7
8 Cell differentiation and stem cells
	Box 8A Conrad Waddington’s ‘epigenetic landscape’ provides a framework for thinking about how cells differentiate
	The control of gene expression
		8.1 Control of transcription involves both general and tissue-specific transcriptional regulators
		8.2 Gene expression is also controlled by epigenetic chemical modifications to DNA and histone proteins that alter chromatin structure
		8.3 Patterns of gene activity can be inherited by persistence of gene-regulatory proteins or by maintenance of chromatin modifications
		8.4 Changes in patterns of gene activity during differentiation can be triggered by extracellular signals
		Summary
	Cell differentiation and stem cells
		8.5 Muscle differentiation is determined by the MyoD family of transcription factors
		8.6 The differentiation of muscle cells involves withdrawal from the cell cycle, but is reversible
		8.7 All blood cells are derived from multipotent stem cells
		8.8 Intrinsic and extrinsic changes control differentiation of the hematopoietic lineages
		Experimental box 8C Single-cell analysis of cell-fate decisions
		8.9 Developmentally regulated globin gene expression is controlled by control regions far distant from the coding regions
		8.10 The epidermis of adult mammalian skin is continually being replaced by derivatives of stem cells
		Medical box 8D Treatment of junctional epidermolysis bullosa with skin grown from genetically corrected stem cells
		8.11 Stem cells use different modes of division to maintain tissues
		8.12 The lining of the gut is another epithelial tissue that requires continuous renewal
		8.13 Skeletal muscle and neural cells can be renewed from stem cells in adults
		8.14 Embryonic stem cells can proliferate and differentiate into many cell types in culture and contribute to normal development in vivo
		Experimental box 8E The derivation and culture of mouse embryonic stem cells
		Summary
	The plasticity of the differentiated state
		8.15 Nuclei of differentiated cells can support development
		8.16 Patterns of gene activity in differentiated cells can be changed by cell fusion
		8.17 The differentiated state of a cell can change by transdifferentiation
		8.18 Adult differentiated cells can be reprogrammed to form pluripotent stem cells
		Experimental box 8F Induced pluripotent stem cells
		8.19 Stem cells could be a key to regenerative medicine
		Experimental box 8G Stem cells can be cultured in vitro to produce ‘organoids’—structures that mimic tissues and organs
		8.20 Various approaches can be used to generate differentiated cells for cell-replacement therapies
		Summary
		Summary to Chapter 8
9 Germ cells, fertilization, and sex determination
	The development of germ cells
		9.1 Germ cell fate is specified in some embryos by a distinct germplasm in the egg
		9.2 In mammals germ cells are induced by cell–cell interactions during development
		9.3 Germ cells migrate from their site of origin to the gonad
		9.4 Germ cells are guided to their destination by chemical signals
		9.5 Germ cell differentiation involves a halving of chromosome number by meiosis
		Box 9A Polar bodies
		9.6 Oocyte development can involve gene amplification and contributions from other cells
		9.7 Factors in the cytoplasm maintain the totipotency of the egg
		9.8 In mammals some genes controlling embryonic growth are ‘imprinted’
		Summary
	Fertilization
		9.9 Fertilization involves cell-surface interactions between egg and sperm
		9.10 Changes in the egg plasma membrane and enveloping layers at fertilization block polyspermy
		9.11 Sperm–egg fusion causes a calcium wave that results in egg activation
		Summary
	Determination of the sexual phenotype
		9.12 The primary sex-determining gene in mammals is on the Y chromosome
		9.13 Mammalian sexual phenotype is regulated by gonadal hormones
		9.14 The primary sex-determining factor in Drosophila is the number of X chromosomes and is cell autonomous
		9.15 Somatic sexual development in Caenorhabditis is determined by the number of X chromosomes
		9.16 Determination of germ cell sex depends on both genetic constitution and intercellular signals
		9.17 Various strategies are used for dosage compensation of X-linked genes
		Summary
		Summary to Chapter 9
10 Organogenesis
	The insect wing and leg
		10.1 Imaginal discs arise from the ectoderm in the early Drosophila embryo
		10.2 Imaginal discs arise across parasegment boundaries and are patterned by signaling at compartment boundaries
		10.3 The adult wing emerges at metamorphosis after folding and evagination of the wing imaginal disc
		10.4 A signaling center at the boundary between anterior and posterior compartments patterns the Drosophila wing disc along the antero-posterior axis
		Box 10A Positional information and morphogen gradients
		10.5 A signaling center at the boundary between dorsal and ventral compartments patterns the Drosophila wing along the dorso-ventral axis
		10.6 Vestigial is a key regulator of wing development that acts to specify wing identity and control wing growth
		10.7 The Drosophila wing disc is also patterned along the proximo-distal axis
		10.8 The leg disc is patterned in a similar manner to the wing disc, except for the proximo-distal axis
		Summary
		10.9 Different imaginal discs can have the same positional values
	The vertebrate limb
		10.10 The vertebrate limb develops from a limb bud and its development illustrates general principles
		10.11 Genes expressed in the lateral plate mesoderm are involved in specifying limb position, polarity, and identity
		10.12 The apical ectodermal ridge is required for limb-bud outgrowth and the formation of structures along the proximo-distal axis of the limb
		10.13 Formation and outgrowth of the limb bud involves oriented cell behavior
		10.14 Positional value along the proximo-distal axis of the limb bud is specified by a combination of graded signaling and a timing mechanism
		10.15 The polarizing region specifies position along the limb’s antero-posterior axis
		10.16 Sonic hedgehog is the polarizing region morphogen
		Medical Box 10B Too many fingers: mutations that affect antero-posterior patterning can cause polydactyly
		10.17 The dorso-ventral axis of the limb is controlled by the ectoderm
		Medical Box 10D Teratogens and the consequences of damage to the developing embryo
		10.18 Development of the limb is integrated by interactions between signaling centers
		10.19 Hox genes have multiple inputs into the patterning of the limbs
		10.20 Self-organization may be involved in the development of the limb
		Box 10E Reaction–diffusion mechanisms
		10.21 Limb muscle is patterned by the connective tissue
		10.22 The initial development of cartilage, muscles, and tendons is autonomous
		10.23 Joint formation involves secreted signals and mechanical stimuli
		10.24 Separation of the digits is the result of programmed cell death
		Summary
	Teeth
		10.25 Tooth development involves epithelial–mesenchymal interactions and a homeobox gene code specifies tooth identity
		Summary
	Vertebrate lungs
		10.26 The vertebrate lung develops from a bud of endoderm
		Medical Box 10F What developmental biology can teach us about breast cancer
		10.27 Morphogenesis of the lung involves three modes of branching
		Summary
	The vertebrate heart
		10.28 The development of the vertebrate heart involves morphogenesis and patterning of a mesodermal tube
	The vertebrate eye
		10.29 Development of the vertebrate eye involves interactions between an extension of the forebrain and the ectoderm of the head
		Summary
		Summary to Chapter 10
11 Development of the nervous system
	Specification of cell identity in the nervous system
		11.1 Initial regionalization of the vertebrate brain involves signals from local organizers
		11.2 Local signaling centers pattern the brain along the antero-posterior axis
		11.3 The cerebral cortex is patterned by signals from the anterior neural ridge
		11.4 The hindbrain is segmented into rhombomeres by boundaries of cell-lineage restriction
		11.5 Hox genes provide positional information in the developing hindbrain
		11.6 The pattern of differentiation of cells along the dorso-ventral axis of the spinal cord depends on ventral and dorsal signals
		11.7 Neuronal subtypes in the ventral spinal cord are specified by the ventral to dorsal gradient of Shh
		11.8 Spinal cord motor neurons at different dorso-ventral positions project to different trunk and limb muscles
		11.9 Antero-posterior pattern in the spinal cord is determined in response to secreted signals from the node and adjacent mesoderm
		Summary
	The formation and migration of neurons
		11.10 Neurons in Drosophila arise from proneural clusters
		11.11 The development of neurons in Drosophila involves asymmetric cell divisions and timed changes in gene expression
		11.12 The production of vertebrate neurons involves lateral inhibition, as in Drosophila
		Box 11A Specification of the sensory organs of adult Drosophila
		11.13 Neurons are formed in the proliferative zone of the vertebrate neural tube and migrate outwards
		Experimental Box 11B Timing the birth of cortical neurons
		Summary
		11.14 Many cortical interneurons migrate tangentially
	Axon navigation
		11.15 The growth cone controls the path taken by a growing axon
		Box 11C The development of the neural circuit for the knee-jerk reflex
		11.16 Motor neuron axons in the chick limb are guided by ephrin–Eph interactions
		11.17 Axons crossing the midline are both attracted and repelled
		11.18 Neurons from the retina make ordered connections with visual centers in the brain
		Summary
	Synapse formation and refinement
		11.19 Synapse formation involves reciprocal interactions
		11.20 Many motor neurons die during normal development
		Medical Box 11D Autism: a developmental disorder that involves synapse dysfunction
		11.21 Neuronal cell death and survival involve both intrinsic and extrinsic factors
		11.22 The map from eye to brain is refined by neural activity
		Summary
		Summary to Chapter 11
12 Growth, post-embryonic development, and regeneration
	Growth
		12.1 Tissues can grow by cell proliferation, cell enlargement, or accretion
		12.2 Cell proliferation is controlled by regulating entry into the cell cycle
		12.3 Cell division in early development can be controlled by an intrinsic developmental program
		12.4 Extrinsic signals coordinate cell division, cell growth, and cell death in the developing Drosophila wing
		12.5 Cancer can result from mutations in genes that control cell proliferation
		12.6 The relative contributions of intrinsic and extrinsic factors in controlling size differ in different mammalian organs
		12.7 Overall body size depends on the extent and the duration of growth
		12.8 Hormones and growth factors coordinate the growth of different tissues and organs and contribute to determining overall body size
		12.9 Elongation of the long bones illustrates how growth can be determined by a combination of an intrinsic growth program and extracellular factors
		Box 12B Digit length ratio is determined in the embryo
		12.10 The amount of nourishment an embryo receives can have profound effects in later life
		Summary
	Molting and metamorphosis
		12.11 Arthropods have to molt in order to grow
		12.12 Insect body size is determined by the rate and duration of larval growth
		12.13 Metamorphosis in amphibians is under hormonal control
		Summary
	Regeneration
		12.14 Regeneration involves repatterning of existing tissues and/or growth of new tissues
		12.15 Amphibian limb regeneration involves cell dedifferentiation and new growth
		Box 12C Regeneration in Hydra
		Box 12D Planarian regeneration
		12.16 Limb regeneration in amphibians depends on the presence of nerves
		12.17 The limb blastema gives rise to structures with positional values distal to the site of amputation
		12.18 Retinoic acid can change proximo-distal positional values in regenerating limbs
		12.19 Mammals can regenerate the tips of the digits
		12.20 Insect limbs intercalate positional values by both proximo-distal and circumferential growth
		Box 12E Why can’t we regenerate our limbs?
		12.21 Heart regeneration in zebrafish involves the resumption of cell division by cardiomyocytes
		Summary
	Aging and senescence
		12.22 Genes can alter the timing of senescence
		12.23 Cell senescence blocks cell proliferation
		12.24 Elimination of senescent cells in adult salamanders explains why regenerative ability does not diminish with age
		Summary
		Summary to Chapter 12
13 Plant development
	13.1 The model plant Arabidopsis thaliana has a short life cycle and a small diploid genome
	Embryonic development
		13.2 Plant embryos develop through several distinct stages
		Box 13A Angiosperm embryogenesis
		13.3 Gradients of the signal molecule auxin establish the embryonic apical–basal axis
		13.4 Plant somatic cells can give rise to embryos and seedlings
		13.5 Cell enlargement is a major process in plant growth and morphogenesis
		Experimental box 13B Plant transformation and genome editing
		Summary
	Meristems
		13.6 A meristem contains a small, central zone of self-renewing stem cells
		13.7 The size of the stem cell area in the meristem is kept constant by a feedback loop to the organizing center
		13.8 The fate of cells from different meristem layers can be changed by changing their position
		13.9 A fate map for the embryonic shoot meristem can be deduced using clonal analysis
		13.10 Meristem development is dependent on signals from other parts of the plant
		13.11 Gene activity patterns the proximo-distal and adaxial–abaxial axes of leaves developing from the shoot meristem
		13.12 The regular arrangement of leaves on a stem is generated by regulated auxin transport
		13.13 The outgrowth of secondary shoots is under hormonal control
		13.14 Root tissues are produced from Arabidopsis root apical meristems by a highly stereotyped pattern of cell divisions
		13.15 Root hairs are specified by a combination of positional information and lateral inhibition
		Summary
	Flower development and control of flowering
		13.16 Homeotic genes control organ identity in the flower
		Box 13C The basic model for the patterning of the Arabidopsis flower
		13.17 The Antirrhinum flower is patterned dorso-ventrally, as well as radially
		13.18 The internal meristem layer can specify floral meristem patterning
		13.19 The transition of a shoot meristem to a floral meristem is under environmental and genetic control
		Box 13D The circadian clock coordinates plant growth and development
		13.20 Vernalization reflects the epigenetic memory of winter
		13.21 Most flowering plants are hermaphrodites, but some produce unisexual flowers
		Summary
		Summary to Chapter 13
14 Evolution and development
	Box 14A Darwin’s finches
	The evolution of development
		14.1 Multicellular organisms evolved from single-celled ancestors
		14.2 Genomic evidence is throwing light on the evolution of animals
		Box 14B The metazoan family tree
		14.3 How gastrulation evolved is not known
		14.4 More general characteristics of the body plan develop earlier than specializations
		14.5 Embryonic structures have acquired new functions during evolution
		14.6 Evolution of different types of eyes in different animal groups is an example of parallel evolution
		Summary
	The diversification of body plans
		14.7 Hox gene complexes have evolved through gene duplication
		14.8 Differences in Hox gene expression determine the variation in position and type of paired appendages in arthropods
		14.9 Changes in Hox gene expression and their target genes contributed to the evolution of the vertebrate axial skeleton
		14.10 The basic body plan of arthropods and vertebrates is similar, but the dorso-ventral axis is inverted
		Summary
	The evolutionary modification of specialized characters
		14.11 Limbs evolved from fins
		14.12 Limbs have evolved to fulfill different specialized functions
		14.13 The evolution of limblessness in snakes is associated with changes in axial gene expression and mutations in a limb-specific enhancer
		14.14 Butterfly wing markings have evolved by redeployment of genes previously used for other functions
		Experimental Box 14C Using CRISPR-Cas9 genome-editing techniques to test the functioning of the snake ZRS
		14.15 Adaptive evolution within the same species provides a way of studying the developmental basis for evolutionary change
		Experimental Box 14D Pelvic reduction in sticklebacks is based on mutations in a gene control region
		Summary
	Changes in the timing of developmental processes
		14.16 Changes in growth can modify the basic body plan
		Box 14E Origins of morphological diversity in dogs
		14.17 Evolution can be due to changes in the timing of developmental events
		14.18 The evolution of life histories has implications for development
		Box 14F Long- and short-germ development in insects
		Summary
		Summary to Chapter 14
Glossary
Index