PART 1. Principles of development in biology
The Questions of Developmental Biology
2. Life cycles and the evolution of developmental patterns
Multicellularity: The Evolution of Differentiation
3. Principles of experimental embryology
4. Genes and development: Techniques and ethical issues
6. Cell-cell communication in development
Paracrine Factors Cell Surface Receptors and Their Signal Transduction Pathways The Cell Death Pathways
Cross-Talk between Pathways
Principles of Development:Cell-Cell Communication References
7. Fertilization: Beginning a new organism
Recognition of Egg and Sperm
Fusion of the Genetic Material
Snapshot Summary: Fertilization References
Early Amphibian Development Axis Formation in Amphibians: The Phenomenon of the Organizer References
Early Development in Fish Early Development in Birds Early Mammalian Development References
12. The central nervous system and the epidermis
14. Paraxial and intermediate mesoderm
15. Lateral plate mesoderm and endoderm
Formation of the Limb Bud
Specification of the Anterior-Posterior Limb Axis The Generation of the Dorsal-Ventral Axis
Cell Death and the Formation of Digits and Joints
Chromosomal Sex Determination in Drosophila
18. Metamorphosis, regeneration, and aging
Aging: The Biology of Senescence
Germ Cell Migration Meiosis Spermatogenesis
PART 4: Ramifications of developmental biology
21. Environmental regulation of animal development
22. Developmental mechanisms of evolutionary change
1. Developmental biology: The anatomical tradition
Anatomical Approaches to Developmental Biology
Medical Embryology and Teratology
Mathematical Modeling of Development
The mathematics of organismal growth
Constant angle of an equiangular spiral and the ratio of widths between whorls
The mathematics of patterning
Principles of Development: Developmental Anatomy
Two. Life cycles and the evolution of developmental patterns
Circle of Life: The Stages of Animal Development
The Evolution of Developmental Patterns in Unicellular Protists
Control of developmental morphogenesis: The role of the nucleus
Unicellular protists and the origins of sexual reproduction
Multicellularity: The Evolution of Differentiation
Differentiation and Morphogenesis in Dictyostelium: Cell Adhesion
Cell adhesion molecules in dictyostelium
Differentiation in dictyostelium
Sex and Individuality in Volvox
Death and Differentiation
Developmental Patterns among the Metazoa
Protostomes and deuterostomes
Principles of Development: Life Cycles and Developmental Patterns
Three. Principles of experimental embryology
Environmental Developmental Biology
Environmental sex determination
Sex determination in a vertebrate: alligator
Adaptation of embryos and larvae to their environments
Protection of the egg by sunscreens and repair enzymes
The Developmental Mechanics of Cell Specification
I. Autonomous specification
II. Conditional specification
III. Syncytial specification
Conditional specification
The influence of neighboring cells
Morphogenesis and Cell Adhesion
Differential cell affinity
The thermodynamic model of cell interactions
Cadherins and cell adhesion
Principles of Development: Experimental Embryology
Four. Genes and development: Techniques and ethical issues
The Embryological Origins of the Gene Theory
The split between embryology and genetics
Early attempts at developmental genetics
Evidence for Genomic Equivalence
Amphibian cloning: The restriction of nuclear potency
Amphibian cloning: The pluripotency of somatic cells
The Exception to the Rule: Immunoglobulin Genes
Differential Gene Expression
RNA Localization Techniques
The polymerase chain reaction
Whole-Mount In Situ Hybridization
Determining the Function of Genes during Development
Gene targeting ("knockout") experiments.
Determining the function of a message: Antisense RNA
Human Somatic and Germ Line Gene Therapy
Identifying the Genes for Human Developmental Anomalies
Principles of Development: Genes and Development
Five. The genetic core of development: Differential gene expression.
Differential Gene Transcription.
Anatomy of the gene: Promoters and enhancers
Examples of transcription factors: MITF and Pax six
Cascades of transcription factors
There are some regions of DNA called locus control regions,
Studying DNA Regulatory Elements
Using enhancers to activate genes
Methylation Pattern and the Control of Transcription
Possible mechanisms by which methylation represses gene transcription
Transcriptional Regulation of an Entire Chromosome: Dosage Compensation
The Mechanisms of X Chromosome Inactivation
Initiation of X Chromosome Inactivation: The Xist Gene
Maintaining X Chromosome Inactivation
Differential RNA Processing
Control of early development by nuclear RNA selection
Creating families of proteins through differential nRNA splicing
Differential nRNA Processing and Drosophila Sex Determination
Control of Gene Expression at the Level of Translation
Differential mRNA longevity
Selective inhibition of mRNA translation
Control of RNA expression by cytoplasmic localization
Epilogue: Posttranslational Gene Regulation
Principles of Development: Developmental Genetics
Six. Cell-cell communication in development
Cascades of induction: Reciprocal and sequential inductive events
Instructive and permissive interactions
Epithelial-mesenchymal interactions
Regional specificity of induction.
Genetic specificity of induction.
The fibroblast growth factors
Cell Surface Receptors and Their Signal Transduction Pathways
The RTK Pathway and Cell-to-Cell Induction
Photoreceptor induction in Drosophila
Vulval Induction in Caenorhabditis elegans
The Nature of Human Syndromes
Cell-Cell Interactions and Chance in the Determination of Cell Types
The Notch pathway: Juxtaposed ligands and receptors
The extracellular matrix as a source of critical developmental signals
Integrins, the cell receptors for extracellular matrix molecules.
Direct transmission of signals through gap junctions
Cross-Talk between Pathways
Principles of Development: Cell-Cell Communication
PARTE Two. Early embryonic development
Recognition of Egg and Sperm
Sperm attraction: Action at a distance
The acrosomal reaction in sea urchins
Species-specific recognition in sea urchins
Gamete binding and recognition in mammals
Induction of the mammalian acrosomal reaction by ZP3.
Secondary binding of sperm to the zona pellucida.
Action at a Distance: Mammalian Gametes
Translocation and Capacitation
Hyperactivation and Chemotaxis
Gamete Fusion and the Prevention of Polyspermy
The prevention of polyspermy
The fast block to polyspermy.
The Activation of Egg Metabolism
The Activation of Gamete Metabolism
Fusion of the Genetic Material
Fusion of genetic material in mammals
The Nonequivalence of Mammalian Pronuclei
Rearrangement of the Egg Cytoplasm
Snapshot Summary: Fertilization
8. Early development in selected invertebrates
An Introduction to Early Developmental Processes
From fertilization to cleavage
The cytoskeletal mechanisms of mitosis
Patterns of embryonic cleavage
Two. MEROBLASTIC (INCOMPLETE CLEAVAGE)
The Early Development of Sea Urchins
Fate maps and the determination of sea urchin blastomeres
Ingression of primary mesenchyme
Importance of extracellular lamina inside the blastocoel
First stage of archenteron invagination
Second and third stages of archenteron invagination
The Early Development of Snails
The polar lobe: cell determination and axis formation
Fate map of Ilyanassa obsoleta
Adaptation by Modifying Embryonic Cleavage
Early Development in Tunicates
Autonomous and conditional specification of tunicate blastomeres
Specification of the embryonic axes
Gastrulation in Tunicates
The second step Early Development of the Nematode Caenorhabditis elegans
Cleavage and Axis Formation in C. elegans
Anterior-posterior axis formation
Formation of the dorsal-ventral and right-left axes
Control of blastomere identity
Conditional specification
Gastrulation in C. elegans
Snapshot Summary: Early Invertebrate Development
Nine. The genetics of axis specification in Drosophila
Early Drosophila Development
The midblastula transition
The Origins of Anterior-Posterior Polarity
The Maternal Effect Genes
The molecular model: protein gradients in the early embryo
Evidence that the bicoid gradient constitutes the anterior organizing center
The posterior organizing center: localizing and activating nanos
The segment polarity genes
The Homeotic Selector Genes
Initiating the patterns of homeotic gene expression
Maintaining the patterns of homeotic gene expression
Cofactors for the Hom-C Genes
The Generation of Dorsal-Ventral Polarity
The Morphogenetic Agent for Dorsal-Ventral Polarity
The Translocation of Dorsal Protein
Signal from the follicle cells to the oocyte cytoplasm.
Establishing the dorsal protein gradient
Effects of the dorsal protein gradient.
Dorsal patterning (repression)
Axes and Organ Primordia: The Cartesian Coordinate Model
Snapshot Summary: Drosophila Development and Axis Specification
10. Early development and axis formation in amphibians
Early Amphibian Development
Cell movements during amphibian gastrulation
The midblastula transition: preparing for gastrulation
Positioning the blastopore
Invagination and involution
The convergent extension of the dorsal mesoderm
Migration of the involuting mesoderm
Fibronectin and the Pathways for Mesodermal Migration
Axis Formation in Amphibians: The Phenomenon of the Organizer
The Mechanisms of Axis Formation in Amphibians
The origin of the Nieuwkoop center
The molecular biology of the Nieuwkoop center
The Functions of the Organizer
Chordin and nodal-related three.
The diffusible proteins of the organizer two: the Wnt inhibitors
Conversion of the ectoderm into neural plate cells
The Regional Specificity of Induction
Molecular correlates of neural caudalization
Three Wnt, FGF, or RA gradient
Specifying the left-right axis
Snapshot Summary: Early Development and Axis Formation in Amphibians
BMP-four and Geoffroy's Lobster
Competence, Bias, and Neurulation
11. The early development of vertebrates: Fish, birds, and mammals
Early Development in Fish
Gastrulation in Fish Embryos
The formation of germ layers
Axis Formation in Fish Embryos
Anterior-posterior axis formation: two signaling centers
Left-right axis formation
Early Development in Birds
Gastrulation of the Avian Embryo
Regression of the primitive streak.
Axis Formation in the Chick Embryo
The role of pH in forming the dorsal-ventral axis
The role of gravity in forming the anterior-posterior axis
Left-right axis formation
Early Mammalian Development
The unique nature of mammalian cleavage
Escape from the Zona Pellucida
Modifications for development within another organism
Formation of extraembryonic membranes
Mammalian Anterior-Posterior Axis Formation
Patterning the anterior-posterior axis: the hox code hypothesis
Expression of hox genes along the dorsal axis
Experimental analysis of the hox code
Retinoic acid teratogenesis.
The Dorsal-Ventral and Left-Right Axes in Mammals
Snapshot Summary: The Early Development of Vertebrates
Twelve. The central nervous system and the epidermis
Formation of the Neural Tube
Formation and shaping of the neural plate.
Bending of the neural plate.
Differentiation of the Neural Tube
The anterior-posterior axis
Ventral patterning of the neural tube.
Dorsal patterning of the neural tube.
Tissue Architecture of the Central Nervous System
Spinal Chord and Medulla Organization
Homologous Specification of Neural Tissue between Vertebrates and Arthropods
Specification of neural ectoderm: The BMP and Dpp and chordin and Sog pathway.
Neural competence: The achaete-scute genes.
Singling out neuronal precursors: The Notch-Delta interaction.
Differentiation of specific neurons.
Development of the Vertebrate Eye
The dynamics of optic development
Neural retina differentiation
Lens and cornea differentiation
The Epidermis and the Origin of Cutaneous Structures
Patterning of cutaneous appendages
Snapshot Summary: Central Nervous System and Epidermis
Thirteen. Neural crest cells and axonal specificity
The mechanisms of trunk neural crest migration
Recognition of surrounding extracellular matrices. Ephrin Neural crest cells
Trunk neural crest cell differentiation
Final differentiation of the trunk neural crest cells.
Neuronal Specification and Axonal Specificity
The Generation of Neuronal Diversity
Pattern Generation in the Nervous System
Guidance by axon-specific migratory cues: the labeled pathways hypothesis
Contact guidance by specific growth cone repulsion
Guidance by diffusible molecules
Address selection: activitydependent development
Differential survival after innervation: neurotrophic factors
Paths to glory: migration of the retinal ganglion axons
Growth of the retinal ganglion axon to the optic nerve.
Growth of the retinal ganglion axon through the optic chiasm.
Adhesive specificities in different regions of the tectum.
The Development of Behaviors: Constancy and Plasticity
Snapshot Summary: Neural Crest Cells and Axonal Specificity
Fetal Neurons in Adult Hosts
Fourteen. Paraxial and intermediate mesoderm
Paraxial Mesoderm: The Somites and Their Derivatives
The initiation of somite formation Periodicity
Specification and commitment of somitic cell types Axial specification
Determination of the sclerotome and dermatome
Determination of the myotome
Myogenesis: The Development of Muscle Specification and differentiation by the myogenic bHLH proteins
Osteogenesis: The Development of Bones
Intramembranous ossification
Endochondral ossification
Control of Cartilage Maturation at the Growth Plate
Fibroblast Growth Factor Receptors
Insulin-like Growth Factors
Extracellular Matrix Proteins
Progression of kidney types
Reciprocal interaction of kidney tissues
The mechanisms of reciprocal induction
Step one: Formation of the metanephrogenic mesenchyme
Step 6: Signals from the mesenchyme induce the branching of the ureteric bud
Snapshot Summary: Paraxial and Intermediate Mesoderm
Fifteen. Lateral plate mesoderm and endoderm
Specification of heart tissue and fusion of heart rudiments
Looping and formation of heart chambers
Formation of Blood Vessels
Constraints on how blood vessels may be constructed
Vasculogenesis: formation of blood vessels from blood islands
Angiogenesis: sprouting of blood vessels and remodeling of vascular beds
The Development of Blood Cells
Pluripotential stem cells and hematopoietic microenvironments
Blood and lymphocyte lineages.
Hematopoietic inductive microenvironments.
Redirecting Blood Flow in the Newborn Mammal
Human embryonic circulation
From fetal to newborn circulation
The Digestive Tube and Its Derivatives
Specification of the gut tissue
The Extraembryonic Membranes
Snapshot Summary: Lateral Mesoderm and Endoderm
The Specification of Liver and Pancreas
Sixteen. Development of the tetrapod limb
Specification of the limb fields: Hox genes and retinoic acid
Induction of the early limb bud: Fibroblast growth factors
Induction of the apical ectodermal ridge
Generating the Proximal-Distal Axis of the Limb The apical ectodermal ridge: The ectodermal component
The progress zone: The mesodermal component
Hox genes and the specification of the proximal-distal axis
Hox Genes and the Evolution of the Tetrapod Limb
Specification of the Anterior-Posterior Limb Axis The zone of polarizing activity
Sonic hedgehog defines the ZPA
The action of sonic hedgehog
The Generation of the Dorsal-Ventral Axis
Coordination among the Three Axes
Cell Death and the Formation of Digits and Joints
Snapshot Summary: The Tetrapod Limb
Seventeen. Sex determination
Chromosomal Sex Determination in Mammals
The mechanisms of mammalian primary sex determination
SRY: the Y chromosome sex determinant
SOX9: autosomal sex reversal
Sf1: the link between sry and the male developmental pathways
Dax1: a potential ovary-determining gene on the X chromosome
Wnt4: a potential ovary-determining gene on an autosome
Testosterone and dihydrotestosterone
Anti-müllerian duct hormone
Sex Determination and Behaviors
Chromosomal Sex Determination in Drosophila The sexual development pathway
The sex-lethal gene as the pivot for sex determination
Maintenance of sxl function
Doublesex: The switch gene of sex determination
Environmental Sex Determination
Location-dependent sex determination in Bonellia and Crepidula
Snapshot Summary: Sex Determination
18. Metamorphosis, regeneration, and aging
Metamorphosis: The Hormonal Reactivation of Development
Amphibian Metamorphosis Morphological changes associated with metamorphosis
Biochemical changes associated with metamorphosis
Hormonal control of amphibian metamorphosis
Regionally specific changes.
Coordination of developmental changes.
Molecular responses to thyroid hormones during metamorphosis
Eversion and differentiation of the imaginal discs
Determination of the Wing Imaginal Discs
Determination of disc identity: vestigial protein
Determination of the anterior-posterior axis: engrailed and decapentaplegic proteins
Dorsal-ventral axis: wingless and apterous proteins
Proximal-distal axis: wingless protein
Hormonal control of insect metamorphosis
The molecular biology of hydroxyecdysone activity
Binding of twenty-hydroxyecdysone to DNA.
Epimorphic Regeneration of Salamander Limbs
Formation of the apical ectodermal cap and
Proliferation of the blastema cells: the requirement for nerves
Pattern formation in the regeneration blastema
Compensatory Regeneration in the Mammalian Liver
Morphallactic Regeneration in Hydras
The head activator gradient.
The head inhibitor gradient.
Basal disc activator and inhibitor gradients.
Medical Advances in Regeneration
Aging: The Biology of Senescence
Maximum Life Span and Life Expectancy
General wear-and-tear and genetic instability
Mitochondrial genome damage.
Snapshot Summary: Metamorphosis, Regeneration, and Aging
19. The saga of the germ line
Germ Plasm and the Determination of the Primordial Germ Cells
Germ cell determination in nematodes
Germ cell determination in insects
Germ cell determination in amphibians
Germ cell migration in mammals
Germ cell migration in birds and reptiles
Germ cell migration in Drosophila
EG Cells, ES Cells, and Teratocarcinomas
Big Decisions: Mitosis or Meiosis? Sperm or Egg?
Maturation of the oocyte in amphibians
Completion of amphibian meiosis: Progesterone and fertilization
Gene transcription in oocytes
Meroistic oogenesis in insects
The structure of the meroistic ovary.
Transport of RNA from nurse cells to oocyte.
Snapshot Summary: The Germ Line
Twenty. An overview of plant development
Gamete Production in Angiosperms
The Vegetative-to-Reproductive Transition
Twenty-one. Environmental regulation of animal development
Environmental Regulation of Normal Development
Predictable Environmental Differences as Cues for Development
Seasonality and sex in aphids
Phenotypic Plasticity: Polyphenism and Reaction Norms
Seasonal polyphenism in butterflies
Environment-dependent sex determination
Polyphenisms for alternative conditions
Predator-Induced Defenses
Mammalian Immunity as a Predator-Induced Response
Learning: An Environmentally Adaptive Nervous System
Experiential changes in inherent mammalian visual pathways
Environmental Disruption of Normal Development
IONIZING RADIATION (X-RAYS)
Retinoic acid as a teratogen
Pathogens as teratogenic agents.
Genetic-Environmental Interactions
Environmental thyroid hormone disruptors
Deformed frogs: pesticides mimicking retinoic acid?
Snapshot Summary: The Environmental Regulation of Development
22. Developmental mechanisms of evolutionary change
"Unity of Type" and "Conditions of Existence"
The search for the Urbilaterian ancestor
Hox Genes: Descent with Modification
The origins of maxillipeds in crustaceans.
Why snakes don't have legs
Assessing Homologies through Regulatory Gene Expression Patterns
How does a new cell type form?
Is the endostyle the precursor of the thyroid gland?
Homologous Pathways of Development
Instructions for forming the central nervous system
Modularity: The Prerequisite for Evolution through Development
Dissociation: Heterochrony and allometry
Duplication and divergence
Developmental Correlation
Coevolution of ligand and receptor
Developmental Constraints
Morphogenetic constraints
Canalization and the Release of Developmental Constraints
A New Evolutionary Synthesis
Snapshot Summary: Evolutionary Developmental Biology
A partial list of genes active in human development