13 - Mesoderm, mechanisms and mutants

Diploblastic

No mesoderm

Caudal dysgenesis (sirenomelia)

Insufficient mesoderm formed

Defects in lower limbs, urogenital system and vertebrae

When does mesoderm form

During gastrulation in the epithelial to mesenchymal transition where cell adhesion molecules are down regulated

Derivatives of intermediate mesoderm

Kidney

Gonads

Derivatives of chordamesoderm

Notochord

Derivatives of paraxial (somitic) mesoderm

Head

Somite - dermatome, endothelial cells, myotome, syndotome, sclerotome

Derivatives of lateral plate mesoderm

Splanchnic

Somatic

Extra-embryonic

Signalling molecule expressed by notochord

Sonic hedgehog Shh

What do somites form from

Paraxial mesoderm

Which end do somites bud from

Anterior end of presomitic mesoderm

What expresses Noggin

Pre-somitic mesoderm

Model in somite formation

Clock and wave front model

Basis of clock and wave model

Somite expression at posterior of post-somitic mesoderm

Expression moves forward

Low levels of ______ allow for somite formation

Fgf8

What is the antagonist of Fgf8 in somite formation

Retinoic acid RA

Example of Notch pathway target

Hairy

What does each oscillation of Hairy in PSM do

Organises PSM cells into pairs of somites

Homeotic mutations

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

Transform one tissue type into another

What stops the heart field from forming medially

Noggin from notochord and somite antagonises BMP

What does heart precursor formation require

Wnt antagonists from the anterior endoderm only

What does the direction of heart looping depend on

Proteins that determine left right asymmetry

Situs inversis

Rare condition where the organs in the chest and abdomen are reversed

What does limb mesenchyme derive from

Myotome and lateral plate mesoderm

Proximodistal outgrowth

Apical ectodermal ridge (AER) and progress zone (PZ)

Anteroposterior patterning

Zone of polarising activity (ZPA)

What is the apical ectodermal ridge (AER)

Ridge of thickened epithelium around the top of the limb bud

Consequence of removing AER

Truncated limb

Role of AER

Keeps limb bud flattened

Needed for limb outgrowth

The progress zone

Distal region of limb bud mesenchyme

Undifferentiated, rapidly dividing cells

What is the progress zone maintained by

AER

What is the role of the progress zone

Limb outgrowth

Organises the AP axis of the limb by releasing a morphogen

What does thalidomide do

Affects cell division in the progress zone

Babies born with shortened limbs

Morphogens

‘Form giving’ substances

Can produce concentration dependent responses in receptive cells

Primary morphogen in patterning limb AP axis

Shh

Mutations in regulatory region of Shh

Lead to limb patterning defects

Shh expressed at anterior and posterior of the limb bud