Development

Development

Development is the process by which a single fertilised egg (zygote) becomes a complex multicellular organism through:

• Cell division

• Cell differentiation

• Morphogenesis (3D organisation)

Early Embryonic Development: Cleavage

• Rapid mitotic divisions without growth

• Produces blastomeres

• Forms a blastula

Key Features:

• No increase in embryo size

• Cytoplasm divided into smaller cells

Early Embryonic Development: Gastrulation

• Major reorganisation phase

• Forms three germ layers

• Establishes body axes

Key Movements:

• Invagination

• Ingression

• Epiboly

Germ Layers and Their Derivatives

Ectoderm

Nervous system, epidermis

Mesoderm

Muscle, bone, blood, kidney

Endoderm

Gut lining, liver, lungs

Induction in Development

Induction = process where:
➡ One group of cells influences the fate of another

4.2 Examples

• Neural induction (ectoderm → neural tissue)

• Lens formation (optic vesicle induces lens)

• Kidney development (reciprocal induction)

Short-range

Direct contact (e.g. Notch signalling)

Long-range

Diffusible signals (morphogens)

Morphogens and Patterning

A morphogen is a signalling molecule that:

• Forms a gradient

• Induces different cell fates at different concentrations

How Gradients Pattern Embryos

• Cells interpret threshold concentrations

• Activate different genes

• Example

• Bicoid gradient (Drosophila)

  • High → anterior structures

  • Low → posterior

TGF-β Signalling

• Secreted signalling proteins

• Regulate:

  • Cell fate

  • Proliferation

  • Patterning

Production

1. Synthesised as inactive precursor

2. Cleaved → mature ligand

3. Secreted as dimer

Receptor Types

• Type I receptors

• Type II receptors

TGF-β Signalling pathway

• Ligand binds Type II receptor

• Type II activates Type I

• Type I phosphorylates Smad proteins

• Smads enter nucleus → regulate genes

Mesoderm Formation (Xenopus)

• Vegetal cells release signals

• Induce overlying cells → mesoderm

Key Regions

• Nieuwkoop Centre (dorsal vegetal)

• Ventral vegetal region

• Organiser (dorsal marginal zone)

Evidence

• Transplant experiments:

  • Organiser induces secondary axis

• Demonstrates:

  • Inductive signalling

Axis Formation: Xenopus vs Drosophila

Feature	Xenopus	Drosophila
Axis formation	Induction-based	Maternal determinants
Key signals	Wnt, TGF-β	Bicoid, Nanos

Hedgehog (Hh) Signalling

• Secreted protein

• Lipid-modified (cholesterol + palmitate)

Pathway Without Hh

• Patched inhibits Smoothened

• Gli repressor active

With Hh

• Hh binds Patched

• Smoothened activated

• Gli activator → gene expression

Wnt Signalling

• Secreted glycoproteins

PathwayWithout Wnt

• β-catenin degraded

With Wnt

• β-catenin stabilised

• Enters nucleus → activates genes

Drosophila Patterning

Segment Polarity Genes

• Wingless (Wg/Wnt)

• Hedgehog (Hh)

Parasegment Boundary Formation

• Two-way signalling:

  • Hh → maintains Wg

  • Wg → maintains Hh

➡ Stable boundary formation

Shh and Wnt in Development & Disease

Development

• Neural tube patterning (Shh)

• Axis formation (Wnt)

Cancer

• Overactive Wnt → colon cancer

• Shh mutations → basal cell carcinoma

Neurulation

• Neural plate → neural tube

Steps:

1. Neural plate forms

2. Folding

3. Closure

Neural Tube Patterning

Shh Gradient

• Ventral → high Shh

• Specifies:

  • Motor neurons

  • Interneurons

Type	Function
Motor neurons	Muscle contraction
Interneurons	CNS communication
DRG neurons	Sensory input
Commissural neurons	Cross midline

Notch Signalling

• Notch receptor

• Delta ligand

Pathway

1. Delta binds Notch

2. Notch cleaved

3. Intracellular domain → nucleus

4. Activates gene expression

Lateral Inhibition

• One cell adopts fate

• Inhibits neighbours

Example

• Sensory organ precursor selection

Axon Guidance

Growth Cones

• Motile structures at axon tips

Guidance Cues

• Attractive (e.g. netrin)

• Repulsive (e.g. semaphorin)

Neuromuscular Junction (NMJ)

Agrin Function

• Secreted by motor neurons

• Induces ACh receptor clustering

Formation Steps

1. Motor neuron contacts muscle

2. Releases agrin

3. Activates MuSK receptor

4. AChRs cluster

5. Synapse stabilises