Lecture 17- Heart development
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What is congenital heart disease?
Structural malformations due to the heart not developing properly during embryogenesis
Give 3 examples of organisms with a similar 4 chambered heart
Human, mice, chicks
Describe the heart structure in xenopus
3 chambered heart
Describe the heart structure in zebrafish
2 chambered heart for a single circulatory system
Describe the heart structure in drosophila
Tubular heart with an enlarged vessel with valves to ensure unidirectional flow
Outline the 4 key morphological steps in heart development
• Cardiac precursor cells found as BILATERAL POPULATIONS of cells around the midline • Migrate to the midline and fuse to form the HEART TUBE • Heart tube undergoes an asymmetric bending morphogenesis termed HEART LOOPING • The heart undergoes MATURATION, resulting in formation of structures required for proper function – valves, septa, trabeculae
Describe the cardiac crescent
A bilateral population of cells which span across the embryos midline and comprises of cardiac precursors
Describe the formation of the heart tube
The migration of cells and fusion of cells at the midline
Define heart looping/loop morphogenesis
Heart tube undergoes asymmetric bending and ballooning
What if formed during heart maturation?
Forming valves between chambers, and connecting to surrounding vasculature
Why does the heart undergo looping?
Reorganising the heart chambers so structures are situated in the correct place and connect properly during maturation
What are the two populations of cardiac cells and which are specified first?
• First heart field - initially incorporated 2. Second heart field - incorporated later
Where are cardiac cells specified in the mouse and the fish?
Mouse- primitive streak Fish- embryonic margin
What signalling is required for the initial specification of the cardiac mesoderm?
Non canonical Wnt signalling
What signalling is required to specific FHF and SHF progenitors?
FHF requires BMP SHF requires canonical Wnt signalling
Once specified, describe the migration of FHF and SHF cells
They migrate anteriorly to form the primitive heart tube (FHF) and SHF in the adjacent mesoderm
What factor does both FHF and SHF cells express?
Nkx2.5
In which ways do cells need to be specified in the heart?
Specify chamber vs non-chamber (e.g. contractile vs non-contractile myocardium) Chamber cells are then specified into atrial vs ventricular contractility (directional conduction) Non-chamber cells are specified by inflow (pacemaker/SA node), atrioventricular canal (valve/ AV node), outflow (valves)
What interaction promotes the specification of the AVC?
BMP2-Tbx2
What interaction promotes the specification of of chamber formation?
Notch-Tbx20
Which myocardium does and does not expand during development?
Non-chamber myocardium does not expand during development Chamber myocardium expands during development to form chambers
Describe the morphology of a Tbx2 mutant mouse and what can be concluded?
Abnormal valve morphology and Nppa expression (chamber marker). They have elongated and non-restricted AVCs Tbx2 required to promote the AVC programme and also required to inhibit chamber formation
Describe the morphology of a Tbx20 mutant mouse and what can be concluded?
A loss of chamber identity (very small dysmorphic chambers), and an expansion of valve markers (Tbx2). Informs us Tbx20 is required for the formation of chambers and inhibits the expression of Tbx2
Describe the morphology of a BMP mutant mouse and what can be concluded?
Have defective AVC development similar to Tbx2 mutants BMP2 mutants have loss of Tbx2 expression therefore BMP2 must be regulating Tbx2 expression