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)
[Lauren Palumbi]

3. Development as Self-Organization
Interesting to Physicists and Mathematicians because largely self-organized not prespecified.
About 5×104 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.

4. Main Processes Cell Differentiation Cell Movement
Cell Proliferation and Death
Cellular Secretion and Absorption of Extracellular Scaffolding

5. 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

6. 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)

7. Homeotic Regulatory Genes

8. Cell Lines Fundamental Distinction:
Germ Cells (immortal) vs. Somatic Cells (disposable)
Germ Layers:
Mesoderm—Muscle, Cartilage, Bone, Germ Cells, Internal Organs (Heart, Blood, Kidneys, ….)
Endoderm—Gut, Lungs, Liver
Ectoderm—Skin, Nervous System

9. 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.

10. Reaction Diffusion Equation (Turing) after Cook & Murray
Two diffusing Species:Activator A; Inhibitor B
Activator-Inhibitor Interactions in Cartilage Pattern Formation

11. Philip Maini

12. 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

13. 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 Filaments—Tensile Strength
Molecular Motors—Myosin, Kinesin, Dynein,…

14. 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.

15. 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

16. Mechanical Changes in Organogenesis

17. 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.

18. Development of Body Plan
Specification of Body Axes
Cleavage
Gastrulation (Formation of Primitive Streak—Anterior-Posterior)
Somitogenesis (Formation of AP compartments)
Organogenesis

19. Initial Axis Determination

20. 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.

21. Types of Cleavage
Holoblastic (entire egg cleaves): usually little yolk in egg.
Isolecithal (symmetric yolk)
Radial—Echinoderms
Spiral—Molluscs
Bilateral—Ascidians/Tunicates (sea squirts, jellyfish)
Rotational—Mammals
Mesolecithal (yolk mostly at one end)
Radial—Amphibians
Bilateral—Cephalopods
Meroblastic (partial cleavage): lots of yolk
Telolecithal (yolk at one end)
Bilateral Discoidal—Reptiles, Fish, Birds
Centrolecithal (yolk in middle)
Superficial—Arthropods
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?

22. Gastrulation (Formation of Germ Layers)

23. Neurulation/Somitogenesis

24. Organogenesis/Limb Development

25. Dictyostelium discoideum

26. Plant Development

27. Lung Development

28. Kidney Development

29. Other Possibilities Vascular Development Bone Development Tumor Growth
Ear (Otic) Development
Liver (Hepatic) Development