20  Developmental Biology and Morphogenesis

20.1 Learning Objectives

By the end of this chapter, you should be able to:

  1. Describe the major stages of animal development from fertilization to organogenesis
  2. Explain how cytoplasmic determinants and inductive signals pattern the embryo
  3. Analyze how gene regulatory networks control developmental processes
  4. Compare and contrast developmental mechanisms across different model organisms
  5. Explain how cells differentiate through selective gene expression and epigenetic modifications
  6. Describe the mechanisms of morphogenesis: cell movement, adhesion, and shape changes
  7. Analyze how developmental pathways have evolved to generate biological diversity
  8. Apply developmental principles to understand birth defects, regenerative medicine, and evolutionary biology

20.2 Introduction

Developmental biology explores how a single fertilized egg transforms into a complex, multicellular organism with precisely arranged tissues and organs. This remarkable process involves intricate coordination of cell division, differentiation, migration, and death, all guided by genetic programs and environmental cues. Understanding development reveals how genes build bodies, how evolution modifies developmental pathways to create diversity, and how errors in development lead to birth defects. This chapter examines the cellular and molecular mechanisms that orchestrate the journey from zygote to adult, connecting genetic information to biological form and function.

20.3 Principles of Development

20.3.1 Fundamental Questions

  1. Differentiation: How do cells with identical genomes become different?
  2. Morphogenesis: How do cells organize into tissues and organs?
  3. Growth: How is size and proportion regulated?
  4. Reproduction: How are gametes formed?
  5. Regeneration: How can some organisms regrow lost parts?
  6. Evolution: How do changes in development create new forms?

20.3.2 Key Concepts

Potency: Cell’s potential to differentiate

  • Totipotent: Can form all cell types plus extraembryonic tissues (zygote)
  • Pluripotent: Can form all embryonic cell types (embryonic stem cells)
  • Multipotent: Can form multiple but limited cell types (adult stem cells)
  • Unipotent: Can form only one cell type (spermatogonia)

Determination: Irreversible commitment to specific fate

Differentiation: Acquisition of specialized structure and function

Pattern formation: Creation of body plan with specific structures in correct locations

Morphogenesis: Physical processes that create tissue shape and organization

20.4 Early Development: Fertilization to Gastrulation

20.4.1 Fertilization

Sperm-egg recognition: Species-specific binding

Acrosomal reaction: Release of enzymes to penetrate egg coat

Fast block to polyspermy: Membrane depolarization

Slow block to polyspermy: Cortical reaction (hardening of vitelline layer)

Activation of egg metabolism: Increased protein synthesis, DNA replication

20.4.2 Cleavage

Rapid cell divisions without growth

Patterns:

  • Radial (echinoderms, amphibians): Symmetrical around animal-vegetal axis
  • Spiral (annelids, mollusks): Diagonal spindle orientation
  • Bilateral (tunicates): Symmetrical along one plane
  • Rotational (mammals): First division meridional, second one meridional and one equatorial

Blastula formation: Hollow ball of cells (blastomeres)

20.4.3 Gastrulation

Rearrangement to form three germ layers

Germ layers:

  • Ectoderm: Nervous system, epidermis, sensory organs
  • Mesoderm: Muscle, bone, circulatory system, kidneys, gonads
  • Endoderm: Gut lining, respiratory tract, liver, pancreas

Gastrulation movements:

  • Invagination: Infolding (sea urchin)
  • Involution: Inward rolling (amphibians)
  • Ingression: Individual cells migrating inward (birds, mammals)
  • Delamination: Splitting of sheet into two layers
  • Epiboly: Spreading of sheet over surface

20.4.4 Axis Formation

Animal-vegetal axis: Established during oogenesis

Dorsal-ventral axis: Determined by sperm entry point (amphibians)

Anterior-posterior axis: Molecular gradients (bicoid in Drosophila)

Left-right asymmetry: Ciliary flow (mammals), Nodal signaling

20.5 Genetic Control of Development

20.5.1 Cytoplasmic Determinants

Maternal effect genes: Expressed in mother, products deposited in egg

  • Establish initial axes and regional identities
  • Examples: bicoid, nanos (Drosophila)

20.5.2 Embryonic Gene Cascades

Segmentation genes (Drosophila model):

  1. Gap genes: Divide embryo into broad regions (hunchback, Krüppel)
  2. Pair-rule genes: Establish alternating segments (even-skipped, fushi tarazu)
  3. Segment polarity genes: Define anterior-posterior within each segment (engrailed, wingless)

Homeotic (Hox) genes: Specify identity of body segments

  • Colinearity: Order on chromosome matches expression along body axis
  • Conservation: Similar genes in all animals
  • Mutations: Transform one body part into another (antennapedia, bithorax)

20.5.3 Induction and Competence

Induction: One tissue influences development of another

  • Inducer: Source of signal
  • Responder: Receives signal
  • Signal molecules: Growth factors, morphogens

Competence: Ability to respond to inductive signal

  • Can be temporally restricted
  • Requires appropriate receptors and intracellular pathways

Morphogen gradients: Concentration-dependent responses

  • French flag model: Different thresholds activate different genes
  • Examples: Bicoid (Drosophila), Sonic hedgehog (vertebrates)

20.5.4 Cell Signaling in Development

Major pathways:

  • Wnt/β-catenin: Cell fate, proliferation, axis formation
  • Hedgehog: Patterning, limb development, neural tube
  • TGF-β/BMP: Dorsal-ventral patterning, organ development
  • FGF: Limb bud outgrowth, neural development
  • Notch: Lateral inhibition, boundary formation

20.6 Cell Differentiation and Stem Cells

20.6.1 Mechanisms of Differentiation

Selective gene expression: Different cells express different subsets of genes

Epigenetic regulation:

  • DNA methylation: Generally repressive
  • Histone modifications: Acetylation (active), methylation (varies)
  • Chromatin remodeling: Changes accessibility
  • Imprinting: Parent-of-origin specific expression

Transcription factor cascades: Master regulators initiate differentiation programs

  • MyoD: Muscle differentiation
  • Pax6: Eye development
  • Sox9: Cartilage formation

20.6.2 Stem Cells

Properties: Self-renewal and differentiation capacity

Types:

  • Embryonic stem cells (ESCs): From inner cell mass, pluripotent
  • Adult stem cells: Tissue-specific, multipotent
  • Induced pluripotent stem cells (iPSCs): Reprogrammed somatic cells

Niche: Microenvironment that maintains stem cell properties

20.6.3 Regeneration

Types:

  • Epimorphosis: Dedifferentiation, proliferation, redifferentiation (salamander limb)
  • Morphallaxis: Remodeling of existing tissue (hydra)
  • Compensatory regeneration: Division of differentiated cells (mammalian liver)

Regeneration vs. scarring: Trade-offs in different organisms

20.7 Morphogenesis: Creating Form

20.7.1 Cell Adhesion and Migration

Cell adhesion molecules (CAMs):

  • Cadherins: Calcium-dependent, homophilic binding (E-cadherin, N-cadherin)
  • Integrins: Bind extracellular matrix (fibronectin, laminin)
  • Selectins: Bind carbohydrates, important in inflammation

Extracellular matrix (ECM): Scaffold for cells, source of signals

  • Collagen: Strength
  • Fibronectin: Cell adhesion, migration
  • Laminin: Basement membranes

Cell migration:

  • Protrusion: Lamellipodia, filopodia
  • Adhesion: New attachments at front
  • Traction: Contraction moves cell body
  • De-adhesion: Release at rear

20.7.2 Cell Shape Changes

Apical constriction: Wedge-shaped cells cause bending (neural tube closure)

Convergent extension: Cells intercalate, tissue narrows and lengthens

Directed cell division: Orientation influences tissue shape

20.7.3 Pattern Formation

Positional information: Cells know their location

Models:

  • French flag (morphogen gradient): Different concentrations specify different fates
  • Reaction-diffusion (Turing): Interactions of activators and inhibitors create patterns (stripes, spots)

Limb development:

  • AER (apical ectodermal ridge): Promotes outgrowth (FGFs)
  • ZPA (zone of polarizing activity): Anterior-posterior patterning (Sonic hedgehog)
  • Progress zone: Proximal-distal patterning

20.8 Organogenesis

20.8.1 Nervous System

Neural induction: Ectoderm → neural plate (organizer secretes BMP inhibitors)

Neurulation: Neural plate → neural tube

  • Primary: Folding and fusion
  • Secondary: Cavitation of solid cord

Neural crest: Migratory cells forming peripheral nervous system, pigment cells, facial bones

Brain regionalization: Forebrain, midbrain, hindbrain

Neurogenesis: Neural stem cells → neurons and glia

20.8.2 Heart Development

Heart field: Mesodermal cells specified to become heart

Heart tube formation: Fusion of bilateral primordia

Looping: Creates chambers and outflow tracts

Septation: Divides chambers and vessels

Valve formation: From endocardial cushions

20.8.3 Limb Development

Limb bud formation: Mesenchyme proliferation with ectodermal covering

Pattern formation: Three axes (proximal-distal, anterior-posterior, dorsal-ventral)

Cartilage models: Replace by bone (endochondral ossification)

Joint formation: Interzones between cartilage elements

Muscle migration: From somites

20.8.4 Other Organs

Kidney: Pronephros → mesonephros → metanephros

Lung: Branching morphogenesis (FGF10)

Gut: Regional specification by Hox genes

Skin: Epidermis (ectoderm) and dermis (mesoderm)

20.9 Growth and Metamorphosis

20.9.1 Growth Control

Determinate growth: Stops at characteristic size (most animals)

Indeterminate growth: Continues throughout life (plants, some animals)

Regulation:

  • Nutritional status: Insulin/IGF pathway
  • Hormones: Growth hormone, thyroid hormone
  • Local factors: Growth factors, mechanical signals

Allometry: Differential growth rates of body parts

20.9.2 Metamorphosis

Definition: Dramatic postembryonic transformation

Amphibians: Thyroid hormone triggers tadpole → frog

  • Tissue remodeling: Tail resorption, limb growth
  • Biochemical changes: Hemoglobin, digestive enzymes

Insects:

  • Holometabolous: Larva → pupa → adult (butterflies, beetles)
  • Hemimetabolous: Nymph → adult (grasshoppers, cockroaches)
  • Hormonal control: Ecdysone (molting), juvenile hormone (maintains juvenile state)

20.10 Evolution and Development (Evo-Devo)

20.10.1 Developmental Constraints

Phylotypic stage: Period when embryos of related species look most similar

Conserved pathways: Same genes used in different contexts

  • Pax6: Eye development in all seeing animals
  • Hox genes: Anterior-posterior patterning in all animals

20.10.2 Generating Diversity

Heterochrony: Change in timing of development

  • Paedomorphosis: Retention of juvenile traits in adult
  • Peramorphosis: Extension of development beyond ancestral state

Heterotopy: Change in location of development

Allometry: Change in growth rates

Gene duplication: New genes can acquire new functions

20.10.3 Case Studies

Limb evolution: Fins → limbs (changes in Hox, FGF, Shh expression)

Snake body plan: Loss of limbs (changes in Hox, Shh expression)

Cichlid jaw diversity: Changes in BMP4 signaling

Butterfly wing patterns: Changes in Wnt, Hedgehog signaling

20.11 Medical Applications

20.11.1 Birth Defects

Teratogens: Agents causing birth defects

  • Thalidomide: Limb defects
  • Alcohol: Fetal alcohol syndrome
  • Retinoic acid: Cranial defects

Genetic causes: Mutations in developmental genes

Multifactorial: Gene-environment interactions

20.11.2 Regenerative Medicine

Tissue engineering: Scaffolds + cells + signals

Stem cell therapies: Replace damaged tissues

Organoids: Mini-organs for disease modeling, drug testing

Reprogramming: Convert one cell type to another

20.11.3 Cancer as Developmental Disease

Oncogenes: Mutated versions of growth-promoting genes

Tumor suppressors: Mutated versions of growth-inhibiting genes

Cancer stem cells: Similar to normal stem cells

Metastasis: Similar to cell migration in development

20.12 Chapter Summary

20.12.1 Key Concepts

  1. Development transforms a single cell into a complex organism through coordinated processes
  2. Cytoplasmic determinants and inductive signals pattern the early embryo
  3. Hierarchical gene cascades (maternal → gap → pair-rule → segment polarity → homeotic) establish body plan
  4. Cell differentiation involves selective gene expression regulated by transcription factors and epigenetic modifications
  5. Morphogenesis creates form through cell adhesion, migration, and shape changes
  6. Organogenesis involves tissue interactions and morphogenetic movements
  7. Evolution acts on developmental processes to generate diversity
  8. Understanding development informs medicine, especially birth defects and regenerative therapies

20.12.2 Stages of Animal Development

Stage Key Events Result
Fertilization Sperm-egg fusion, egg activation Zygote
Cleavage Rapid cell divisions Blastula (blastocyst in mammals)
Gastrulation Cell movements, germ layer formation Gastrula with three germ layers
Neurulation Neural tube formation Beginning of nervous system
Organogenesis Organ formation Functional organs
Growth & maturation Size increase, functional maturation Adult organism

20.12.3 Germ Layers and Derivatives

Germ Layer Major Derivatives
Ectoderm Nervous system, epidermis, hair/nails, lens of eye, inner ear, pituitary gland
Mesoderm Muscle, bone, cartilage, blood, blood vessels, kidneys, gonads, dermis
Endoderm Lining of digestive and respiratory tracts, liver, pancreas, thyroid, bladder

20.12.4 Key Developmental Genes

Gene Class Function Examples
Maternal effect Establish initial axes bicoid, nanos (Drosophila)
Gap genes Define broad regions hunchback, Krüppel
Pair-rule genes Establish alternating segments even-skipped, fushi tarazu
Segment polarity Define anterior-posterior within segments engrailed, wingless
Homeotic (Hox) Specify segment identity Antennapedia, Ultrabithorax
Morphogens Concentration-dependent patterning Bicoid, Sonic hedgehog

20.12.5 Major Signaling Pathways in Development

Pathway Key Components Developmental Roles
Wnt/β-catenin Wnt, Frizzled, β-catenin Axis formation, cell fate, proliferation
Hedgehog Shh, Patched, Smoothened Neural tube, limb patterning, left-right asymmetry
TGF-β/BMP BMP, TGF-β, Smads Dorsal-ventral patterning, organ development
FGF FGF, FGFR, Ras/MAPK Limb outgrowth, neural development
Notch Notch, Delta, Hes genes Lateral inhibition, boundary formation

20.12.6 Model Organisms in Developmental Biology

Organism Advantages Key Contributions
Drosophila melanogaster (fruit fly) Genetics well understood, rapid development Genetic control of development, homeotic genes
Caenorhabditis elegans (nematode) Cell lineage completely mapped, transparent Programmed cell death, cell signaling
Danio rerio (zebrafish) Transparent embryo, genetic manipulation Vertebrate development, live imaging
Xenopus laevis (frog) Large eggs, easy manipulation Embryonic induction, axis formation
Mus musculus (mouse) Mammalian, genetic tools available Mammalian development, human disease models
Arabidopsis thaliana (plant) Plant model, small genome Plant development, pattern formation

20.13 Review Questions

20.13.1 Level 1: Recall and Understanding

  1. List and describe the three germ layers and their major derivatives.
  2. What are the main stages of animal development from fertilization to organ formation?
  3. Define the terms: totipotent, pluripotent, multipotent, and unipotent.
  4. Explain the difference between determination and differentiation.
  5. What is a morphogen gradient and how does it work (French flag model)?

20.13.2 Level 2: Application and Analysis

  1. If bicoid mRNA is injected into the anterior end of a Drosophila embryo with a bicoid mutation, what happens? What if injected into the posterior end?
  2. How does the process of neural tube closure illustrate the principle of morphogenesis through cell shape changes?
  3. Compare and contrast regeneration in hydra (morphallaxis) and salamander limbs (epimorphosis).
  4. Explain how heterochrony (changes in developmental timing) can lead to evolutionary changes in body form.
  5. How do Hox genes illustrate the principle of colinearity, and what happens when their expression is altered?

20.13.3 Level 3: Synthesis and Evaluation

  1. Design an experiment to test whether a particular signaling molecule acts as a morphogen during limb development.
  2. Evaluate the hypothesis that cancer can be understood as a disease of development gone awry.
  3. How might knowledge of developmental biology contribute to treatments for spinal cord injuries?
  4. Propose an explanation for why certain organs (like the heart) form very early in development while others (like reproductive organs) form much later.

20.14 Key Terms

  • Development: Process by which a multicellular organism grows and differentiates from a single cell
  • Differentiation: Process by which cells become specialized in structure and function
  • Morphogenesis: Developmental process that gives a tissue, organ, or organism its shape
  • Gastrulation: Embryonic stage during which the three germ layers form
  • Ectoderm: Outermost germ layer; gives rise to nervous system and epidermis
  • Mesoderm: Middle germ layer; gives rise to muscle, bone, and circulatory system
  • Endoderm: Innermost germ layer; gives rise to gut and associated organs
  • Induction: Process by which one group of cells influences the development of adjacent cells
  • Morphogen: Substance that governs pattern formation by forming a concentration gradient
  • Homeotic genes: Genes that control the identity of body parts
  • Stem cell: Cell that can both self-renew and differentiate into specialized cell types
  • Totipotent: Ability of a cell to give rise to all cell types of an organism
  • Pluripotent: Ability of a cell to give rise to all embryonic cell types
  • Determination: Point at which a cell’s developmental fate becomes fixed
  • Pattern formation: Process by which cells in a developing embryo acquire identities that lead to a well-ordered spatial pattern
  • Apoptosis: Programmed cell death; important in development

20.15 Further Reading

20.15.1 Books

  1. Gilbert, S. F., & Barresi, M. J. F. (2020). Developmental Biology (12th ed.). Sinauer Associates.
  2. Wolpert, L., Tickle, C., & Martinez Arias, A. (2019). Principles of Development (6th ed.). Oxford University Press.
  3. Carroll, S. B. (2005). Endless Forms Most Beautiful: The New Science of Evo Devo. W. W. Norton.

20.15.2 Scientific Articles

  1. Nüsslein-Volhard, C., & Wieschaus, E. (1980). Mutations affecting segment number and polarity in Drosophila. Nature, 287(5785), 795-801.
  2. Spemann, H., & Mangold, H. (1924). Über Induktion von Embryonalanlagen durch Implantation artfremder Organisatoren. Wilhelm Roux’ Archiv für Entwicklungsmechanik der Organismen, 100(3), 599-638.
  3. Takahashi, K., & Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126(4), 663-676.

20.15.3 Online Resources

  1. The Virtual Embryo: https://www.ucalgary.ca/UofC/eduweb/virtualembryo
  2. Developmental Biology Online: https://www.devbio.com
  3. Evo-Devo resources: https://www.evodevojournal.org
  4. Stem Cell Information (NIH): https://stemcells.nih.gov

20.16 Quantitative Problems

  1. Morphogen Gradient: A morphogen is produced at the anterior end of an embryo and diffuses posteriorly. Production rate = 100 molecules/µm²/s Diffusion coefficient = 10 µm²/s Degradation rate = 0.1/s
    1. Write the reaction-diffusion equation for this system.
    2. What is the steady-state concentration profile?
    3. How far from the source does the concentration drop to 10% of its maximum?
    4. If three genes are activated at thresholds of 50%, 20%, and 5% of maximum concentration, where along the axis will each be expressed?
  2. Cell Lineage Analysis: In C. elegans, the entire cell lineage is known. From the zygote:
    • First division gives AB and P1
    • AB divides into ABa and ABp
    • P1 divides into EMS and P2
    • EMS divides into E and MS
    • etc. If each cell division takes 30 minutes, and the adult has 959 somatic cells:
    1. How many cell divisions occurred?
    2. How long did development take (assuming synchronous divisions)?
    3. What percentage of cells undergo apoptosis during development?
  3. Pattern Formation: In a reaction-diffusion system (Turing mechanism):
    • Activator: a, diffuses slowly, activates itself and inhibitor
    • Inhibitor: b, diffuses rapidly, inhibits activator Parameters: da/dt = f(a,b) + Da∇²a, db/dt = g(a,b) + Db∇²b where f and g are nonlinear functions.
    1. Under what conditions (Da, Db) will patterns form?
    2. What determines the wavelength (spacing) of patterns?
    3. How might this model explain zebra stripes or leopard spots?

20.17 Case Study: Thalidomide Tragedy

Background: In the late 1950s and early 1960s, thalidomide was prescribed as a sedative and anti-nausea drug for pregnant women. It caused severe birth defects, particularly limb malformations, in thousands of babies worldwide.

Questions:

  1. What specific developmental processes does thalidomide disrupt in limb formation?
  2. Why was thalidomide teratogenic in humans but not in many animal models initially tested?
  3. How does this tragedy illustrate the importance of critical periods in development?
  4. What regulatory changes resulted from this tragedy?
  5. Ironically, thalidomide is now used to treat certain cancers and leprosy. How can the same drug be both teratogenic and therapeutic?

Data for analysis:

  • Critical period: Days 20-36 of gestation for limb defects
  • Mechanism: Inhibits angiogenesis, binds to cereblon protein affecting limb outgrowth
  • Species differences: Rabbits and primates sensitive, mice and rats less sensitive
  • Current use: Multiple myeloma, leprosy (with strict pregnancy prevention)
  • Regulatory impact: Led to stricter drug testing requirements worldwide

Next Part: Part VI: Frontiers in Biology