Introduction to Developmental Biology

1
Introduction to Developmental Biology

• Mathematical Biology Lecture 3
• James A. Glazier
• (All Uncredited Figures From Wolpert et al.
  Principles of Development)

2
Development in Ninety Minutes

• What is Development?
• Biological Process by Which a
• Fertilized Egg ? Organism
• Physical Process Which Translates
• Genetic Information (Genotype)
• ?
• Structure and Behavior (Phenotype)

3
Development as Self-Organization

• Interesting to Physicists and Mathematicians
  because largely self-organized not prespecified.
• About 5104 genes and 109 cells. Genome does not
  contain enough information to specify each cell.
• Even if it did, development would be fragile if
  completely specified.
• Instead, highly robust at all levels.

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Main Processes

• Cell Differentiation
• Cell Movement
• Cell Proliferation and Death
• Cellular Secretion and Absorption of
  Extracellular Scaffolding

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Differentiation

• One Cell Type Initially, Many in Adult
• All Cells Have the Same Genes (modulo immune
  cells)
• Cell Type Determined by Epigenetic Effects
• Pattern of Gene Expression
• Internal Structure
• Metabolic Factors

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Gene Switching

• Promoters Turn On Repressors Turn Off Translation
  of Genes into Messenger RNA (mRNA)
• Can Also Regulate the Lifetime of mRNA and the
  Translation of mRNA into Proteins
• More Exotic Regulation as Well
• Regulation has Complex Feedback and Interactions
  in the Gene Regulatory Network
• Enzymes can Methylate Stretches of DNA Turning
  Genes off Permanently
• Hence Differentiation is Usually a One-Way
  process Less Differentiated?More Differentiated
• Opposite Ends of Spectrum Stem Cells, Terminally
  Differentiated Cells (e.g. Neurons)

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Homeotic Regulatory Genes
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Cell Lines
Fundamental Distinction Germ Cells (immortal)
vs. Somatic Cells (disposable) Germ
Layers MesodermMuscle, Cartilage, Bone, Germ
Cells, Internal Organs (Heart, Blood, Kidneys,
.) EndodermGut, Lungs, Liver EctodermSkin,
Nervous System
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How Does a Cell Know What to Differentiate Into?

• Cell Does Not Carry a Road Map! Only Knows its
  Own Composition and Local Environment.
• Positional Information
• Part of the Cytoplasm in the Egg from Which Cell
  Derived.
• Contact With Other Cells or Substrate.
• Reception of Extracellular Diffusants.
• Previous Differentiation History of Cell.

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Reaction Diffusion Equation (Turing) after Cook
Murray

• Two diffusing SpeciesActivator A Inhibitor B

Activator-Inhibitor Interactions in Cartilage
Pattern Formation
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Philip Maini
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Consequences of Differentiation

• Cells
• Change Shape
• Polarize (Become Asymmetric)
• Move
• Divide/Die
• Send and Respond to Chemical and Electrical
  Signals
• Secrete and Absorb Extracellular Material

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Cell Shape Changes

• Determined by Cytoskeleton
• Microfilaments (Actin)Cell Movement, Force
  Generation, Cell Division.
• Microtubules (Tubulin)Compressive Strength, Cell
  Shape and Polarization, Chromosome Separation,
  Long-range Transport inside Cell.
• Intermediate FilamentsTensile Strength
• Molecular MotorsMyosin, Kinesin, Dynein,

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Cell Polarization

• Localization of Receptors and Junctions on
  Surface of Cell.
• Asymmetry of Cytoskeleton.
• E.g. of Egg (Animal and Vegetal Poles), Neuron
  (Axon, Dendrite and Soma).
• Most Cells form Monolayer Sheets (Epithelia).
• Epithelial Cells have Different Properties on
  their Apical, Basal and Lateral Surfaces. They
  Bind Tightly to their Neighbors and Variably on
  their Tops and Bottoms.
• Mesenchymal Cells are More Symmetrical and Form
  Connective Tissue.

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Cell Movement
Cells Move Long Distances During
Development. Move by Protruding and Retracting
Filopodia or Lamellipodia (Leading Edge) Shape
Changes During Movement May be Random or
Directed. Move By Sticking Selectively to Other
Cells (Differential Adhesion) Move By Sticking
to Extracellular Material (Haptotaxis) Move By
Following External Chemical Gradients
(Chemotaxis) Can also have Bulk
Movement Secretion of ECM Differential Cell
Division Oriented Cell Division
Chemotaxis Play Movies
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Mechanical Changes in Organogenesis
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Feedback Loops

• Not Simply Signal?Differentiation?Pattern (Known
  as Prepatterning).
• Cells Create Their Own Environment, by Moving and
  Secreting New Signals, so Signaling Feeds Back on
  Itself.
• Hence Self-Organization and Robustness.

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Development of Body Plan

• Specification of Body Axes
• Cleavage
• Gastrulation (Formation of Primitive
  StreakAnterior-Posterior)
• Somitogenesis (Formation of AP compartments)
• Organogenesis

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Initial Axis Determination
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Cleavage Basics

• Period of rapid cell division (up to once every
  ten minutes).
• No cell growth (no interphase).
• Karyokinesis (Chromosome replication) and
  Cytokinesis (Cell division) may occur separately.
  
• Cytokinesis may be missing or partial.
• Karyokinesis and Cytokinesis are usually
  synchronous throughout the embryo.
• Little or no relative cell movement.
• Many types in different species.

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Types of Cleavage

• Holoblastic (entire egg cleaves) usually little
  yolk in egg.
• Isolecithal (symmetric yolk)
• RadialEchinoderms
• SpiralMolluscs
• BilateralAscidians/Tunicates (sea squirts,
  jellyfish)
• RotationalMammals
• Mesolecithal (yolk mostly at one end)
• RadialAmphibians
• BilateralCephalopods
• Meroblastic (partial cleavage) lots of yolk
• Telolecithal (yolk at one end)
• Bilateral DiscoidalReptiles, Fish, Birds
• Centrolecithal (yolk in middle)
• SuperficialArthropods
• Query How can closely related families differ so
  radically at the very earliest stages of
  development? How could they have changed their
  developmental programs in a non-lethal way?

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Gastrulation (Formation of Germ Layers)
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Neurulation/Somitogenesis
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Organogenesis/Limb Development
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Dictyostelium discoideum
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Plant Development
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Lung Development
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Kidney Development
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Other Possibilities

• Vascular Development
• Bone Development
• Tumor Growth
• Ear (Otic) Development
• Liver (Hepatic) Development