Gastrulation and segmentation in vertebrate embryos

Establishment of the basic body plan

Symmetry and segmentation of vertebrates

Vertebrates are bilaterians- animals with bilateral symmetry

• anterior: posterior (AP) body axis

Serial repetition of parts along the body axis = segmentation

Gastrulation and the formation of the 3 germ layers

During gastrulation cells from the epiblast migrate into the primitive streak

Here they undergo an epithelial to mesenchymal transition and migrate under the epiblast

These cells give rise to the endoderm and the mesoderm

Gastrularion and the formation of the 3 germ layers

Germ layers

Structure of the embryo

Segmentation

Segmental organisation is found in many diverse animal groups including vertebrates

Segmentation is an efficient way to generate diverse body parts from similar basic structures during development

Somites develop from unsegmented mesoderm

Somites are balls of epithelial tissue that bud off from the unsegmented paraxial mesoderm

They start forming at the anterior end and are added to the posterior

They form in a regular pattern with a set periodicity (1 every 90 mins in chickens, 1 every 2 hrs in mice)

Axis extension

The axial skeleton (with the exception of the skull) arises from somites

Somites start to form at the anterior end of the embryo and are then added in pairs:

• sequentially

• periodically

Fibroblast growth factors (FGFs) control cell motility and elongation of the embryo

Example

FGF8 is expressed in a gradient in paraxial mesoderm = PSM

Experiment to show that FGFs play a role in normal somite formation

Experiment to show that FGFs play a role in normal somite formation pt2

High concentrations of FGF in the posterior inhibit the formation of somites

Decay of FGF mRNA produced a gradient of FGF

At low concentrations (anterior) somites can form

However, this does not explain the precise timing of somite formation

Another component is required to act as a ‘clock’ to generate this periodicity

Component of the segmentation/ somite clock

Hes1 is cyclically expressed in presomitic mesoderm (PSM)

Hes1 is a transcription factor

It is a vertebrate homolog of the hairy gene in Drosophilia

This contributes the somite segmentation clock

Segmentation summary

Segmentation produces a repeated array of tissues along the embryonic axis

This is controlled by a ‘clock and wavefront’ process producing regular pulses of segmental activity- originally proposed as a theoretical model of segmentation

Segmental identity

Each segment has a specific indentity which determines the nature of the tissues being formed

This is clearly seen in the vertebrae- cervical vertebrae lack rib attachments for example

In any species this pattern is highly conserved

Segmental identity is determined before segmentation

If pre- segmented mesoderm is grafted to a different position along the axis it retains its original identity

E.g. thoracic level mesoderm will form thoracic vertebrae with ribs

How genes play a key role in establishing of the morphological identity of somites and the vertebrae

How genes encode transcription factors

Regular aspects of morphogenesis in animals

Evolutionarily conserved

How gene → target gene

Hox genes in diverse animals

Comparison of hot genes in Drosophila and mice shows a remarkable degree of conservation of this mechanism

Hox genes are used across the animal kingdom to define region of the animal

How gene expresion domains and vertebral formula of the mouse embryo

Segmental identity

Although related species show similar patterns there are differences

These differences are 1 way that evolution can generate differences between species

Mice (and all mammals except sloths and manatees) have 7 cervical vertebrae. Chickens have 14, swans 25 and elasmosaurus had 76

Segmental identity and gene expression patterns

Changes in veterbral identity correlate with boundaries of expression of homeobox (Hox) genes

This can explain changes in vertebral patterning e.g. more cervical vertebrae in birds correlate with longer expression domains of anterior hot genes

Mutations in how genes

Further evidence for the role of hot genes has come from mouse knockouts

In mice where hot genes have been mutated changes in the identity of vertebrae are seen

Mice lacking the hox 10 genes show lumbar to thoracic transformations, mice lacking hot 11 genes show sacral to lumbar changes

Linking gastrulation and axis patterning

Hox genes are differentially expressed in the primitive streak

Cells expressing anterior hot genes are only found in the early streak and the anterior mesoderm

More posterior hox genes are expressed in the streak for longer but are not seen in the anterior mesoderm even though cells in the streak express these genes

Linking gastrulation and axis patterning

The control of axial identity is linked to gastrulation

Cells expressing more posterior hot genes leave the streak later and form more posterior somites

Summary

The anterior- posterior axis in vertebrates is organised segmentally

These segments are generated by sequential addition of somites

This identity is determined during gastrulation as cells emerge from the primitive streak