Cardiogenesis Flashcards
Give a brief and simple overview of the heart circulation system
Atria receives blood, flows to ventricles and to pulmonary system (oxygen)
Flows back in to left side of heart and then through circulation of the body
What are the time stamps for human heart development?
- 3 weeks post fertilisation - heart tube is formed
- 31 days - Looping morphogenesis: heart tube forms a S helical shape
- 5 weeks - formation of the chambers and atrial appendages
- 6 weeks - emergence of the ventricles
- 56 days - Functional maturation, reaching the final stage of development
THEN IT JUST GETS BIGGER
What are the differences between model organisms studied for cardiogenesis?
Mice + Chicks:
- Both have four chambers but mice develop internally (hard to observe)
Xenopus + Zebrafish + Drosophila
- Xeno only have 1 ventricle
- Zebrafish have 2 chamber heart with single circulatory system
- Drosophila just baso has a ‘fancy blood vessel’ and valves - good to study earlyyy formation
What is the morphological timeline of the heart?
- Cardiac precursor cells found as bilateral populations of cells around midline
- Migrate to midline + fuse to form heart tube
- Driven by convergent extension (conserved across species)
- Heart tube undergoes an asymmetric bending morphogenesis called ‘heart looping’
- The heart then undergoes maturation resulting in the formation of valves, septa, ballooning of chambers etc.
Explain the origin of cardiac cells
- Form from mesodermal cells along the primitive streak which undergo differentiation from combinatorial signalling to form cardiac progenitor cells
- They migrate to midline of embryo forming a crescent- shaped structure
- First heart field cells (FHFcs) contribute to initial heart tube formation and are at the anterior of the crescent
- Second heart field cells (SHFcs) contribute to elongation and looping , located at posterior
What controls whether the cardiac progenitor cells will be FHFcs or SHFCs?
FHFcs = Wnt and BMP
SHFcs = receive Wnt/FGF
What causes the differentiation between contractile and non-contractile regions in heart development?
- Being set up in the heart tube
Notch-Tbx20 pathway activates chamber-specific genes
BMP- Tbx2 pathway induces expression of genes only in the atrioventricular canal (no beating)
What is the phenotype of Tbx2 mutant mice?
- abnormal atrioventricular canal morphology
- expansion of the chamber specific marker which makes their AVC look more like a chamber than a canal
What is the phenotype of Tbx20 mutant mice?
- no chamber specific markers
- hyper expansion of Tbx2 expression meaning there is less chamber and more of the AVC canal
SHOWS THERE IS A BALANCE BETWEEN TBX20 AND TBX2
Explain the process of heart looping morphogenesis
- Iselt1 expressed in SHFcs in the mesoderm adjacent to the heart
- Lacz tracing to see where cells have been that have expressed specific genes previously
-Iselt1 expressing cells are now in the heart meaning the SHF cells are being deployed into the heart as the heart is undergoing morphogenesis, increasing the size of the heart - NOT DUE TO PROLIFERATION
Why is left/right asymmetry of the heart important?
- condition called situs inversus where internal organs are flipped the other way round
- heterotaxia = different things in different places
Where is Nodal expressed?
left lateral plate mesoderm of embryos prior to embryo formation
How does cardiac disc in zebrafish undergo rotation and involution to form a tube?
- Node is a cupshaped and at posterior
- Full of cilia which can undergo rotation v. quickly
- Nodal flow leads to asymmetrical upregulation of nodal gene on the left lateral plate mesoderm (called spaw?)
- Nodal genes are expressed in the left half of the cardiac disc
- Cardiac disc undergoes rotation and involution to form a tube
What can randomisation of lateralised gene expression cause?
- describing essentially a loss of nodal flow
- lead to abnormal asymmetry congenital defects in the heart
