Stages of Development

Question 1

1. Gastrulation

Answer 1

• Formation of the 3 germ layers (echo/meso/endoderm)
• Ectorderm cells migrate down primitive streak and splanchnic LPM arises
• Bilateral endothelial tubes form

Question 2

2. Fusion

Answer 2

• Folding of the embryo causes the foregut to close
• The bilateral endothelial tubes are brought together
• The lateral cells form the initial heart tube in the midline
• Fusion occurs anterior/cranially to posterior/caudally

Question 3

3. Left-Right axis

Answer 3

• Signalling node develops asymmetry (ion channel and other gene expression)
• Asymmetric migration of cells around the node
• Cilia thought to direct R-L flow of vesicles signalling to LPM
  (Kartagener Syndrome: immobile cilia => heart defects)

Question 4

3. i) Left

Answer 4

• Shh expression causes release of nodal
• Nodal diffuses fast through ECM to left LPM
• Nodal signal amplified/reproduced here and induces Pitx2

Question 5

3.ii) Right

Answer 5

• BMP4 expression causes release of FGF8
• FGF8 activates SnR, which inhibits Pitx2 on the right
• BMP2 activates ActRIIA

Question 6

Pitx2

Answer 6

• ONLY on left side, before and after looping
• Important in left atrium, suppresses left-SAN formation
  (AF in adults due to ectopic ion channel expression)
• Promotes atrial septation
• Not important in looping (k/o still loops)

Question 7

Prrx1a

Answer 7

• Relative (more) right sided expression

- Recently shown to be required for right-sided looping

Question 8

4. Chamber formation

Answer 8

• During looping, chamber myocardium rapidly proliferates in the ventricular compartment and then the atrium
• SHF cells at V pole form RA, here cells with fastest depolarisation originate the heart beat
• Nkx2.5, Tbx5 and Pitx2 are important