13 - Mesoderm, mechanisms and mutants

Mesoderm

• Middle of the three germ layers 

• Diploblastic - no mesoderm

• Eg. jellyfish, coral, sea anemones 

Caudal dysgenesis (sirenomelia) 

• Insufficient mesoderm formed 

• Defects in lower limbs, urogenital system, vertebrae

Brachyury mutant mice 

• Brachyury required for mesoderm differentiation 

• Homozygotes lack a trunk and tail and die around embryonic day 10

• Heterozygotes - short tail and abnormal vertebrae 

Embryonic origin of mesoderm 

• Forms during gastrulation 

• Epithelial to mesenchymal transition (EMT)

• Cell adhesion molecules down-regulated

Chick mesoderm formation

Types of mesoderm 

Derivatives of the mesoderm 

Chordamesoderm: the Notochord 

• Early forming midline structure 

• Transient 

• Signalling centre / organiser 

Blue = notochord

Green = somites

Red = intermediate mesoderm 

Structures notochord patterns include:

• Neural tube (ectoderm)

• Somites (mesoderm)

Expressed signalling molecule = Sonic hedgehog (Shh)

Zebrafish notail (ntl) mutants lack a notochord: 

• Abnormal neural tube 

• Abnormal somites / muscle 

Somites 

• Form from paraxial mesoderm 

• Form in pairs 

• Characteristic number for each species 

• Form anterior to posterior 

• Bud off from anterior end of presomitic mesoderm 

Specification of the somite forming region (paraxial mesoderm)

Somite formation (chick) 

Regulation of somite formation 

• Clock and wave front model 

• Expressed at the posterior of the post-somitic mesoderm and moves forward - the cells do not move - only the expression does

• More than one oscillation going on at once 

1. Fgf8 gradient from the posterior of the presomitic mesoderm (PSM) 

2. Somites form at a specific (low) level of Fgf8

3. Antagonised by retinoic acid (RA) from somites 

The clock - controls somite segmentation 

• Expression of Notch pathway targets (eg. hairy) oscillates in the PSM 

• Each oscillation organises pre somitic mesoderm (PSM) cell into pairs of somites 

Chick: 

Clock and wave front model 

• Integrated - the clock only functions to form somites at specific (low) levels of Fgf8

Anterior - posterior specification of somites 

• Somites are specialised along AP axis 

• AP identity specified by Hox code 

Experimental evidence 

• Change in Hox gene expression patterns lead to changes in segment identity 

• Eg. Hox10 KO mouse 

• Lumbar to thoracic identity

Homeotic mutations - Transform one tissue type into another 

• Changes in expression of ‘Master control’ genes that confer identity to individual segments 

Flies exhibiting homeotic transformations

→ Adult fly heads: wild type and antennapedia 

• (Antp - antennae transformed to 2nd thoracic leg)

→ Adult flies: wild type and bithorax mutant (haltere transformed to wings; transformation of 3rd thoracic segment to 2nd thoracic segment) 

Changes in expression of two genes in two complexes 

Hox gene conservation from flies to vertebrates 

Changes in Hox gene expression lead to changes in neck length 

→ The chick has twice as many and cervical (neck) vertebrae as the mouse

→ Caused by changes in Hox gene expression 

Loss of snake forelimbs 

• Hoxc6 expanded - inhibits forelimb development 

• Different mechanism for posterior limb loss 

Summary 

• Specification of presomitic mesoderm - Noggin v Bmp

• Specification of somite identity along the AP axis - HOXs - homeosis

• Formation of somites - Clock and wave front model