CV Development: Congenital Heart Dis.

Question 0

Where are the cardiac precursor cells on the embryonic disc?

Answer 0

In the “cardiac crescent”

Question 1

5 major processes that occur in cardiovascular morphogenesis?

Answer 1

Myocardial specification and formation of linear heart tube.
Looping.
Septation.
Patterning of great vessels.
Circulatory changes at birth.

Question 2

What connects the linear heart tube to the aorta /other vessels?

Answer 2

The dorsal mesocardium.

Question 3

Does the early heart make some of its own blood?

Answer 3

We think so.

Question 4

Are heart chambers pre-specified in the linear heart tube?

Answer 4

Yes, to some extent. (but there’s also the secondary heart field)

Question 5

Where is the “second heart field”?

Answer 5

The second heart field progenitor cells come from the pharynx. (worms have rhythmically contracting guts)

Question 6

What does looping refer to?

Answer 6

the atria start at the bottom, and loop up to the top.

Question 7

What’s the bulbus cordis?

Answer 7

The region made of the conus cordis (outflow tract) and truncus arteriosis (PA and aorta)

Question 8

How does the AV canal form?

Answer 8

It’s a section of the tube that doesn’t grow… so constricted by comparison.
This also forms the endocardial cushions…

Question 9

What’s the first part of atrial septation?

Answer 9

The septum primum forms on the dorsal wall and grows toward the endocardial cushions.

Question 10

Does the septum primum entirely separate the LA and RA?

Answer 10

Nope, it leaves the ostium primum near the endocardial cushions.

Question 11

What happens next when there’s a septum primum with ostium primum?

Answer 11

Holes form in the dorsal aspect of the septum primum, forming the ostium secundum.
Then the septum secundum passively covers the RA side of the septum primum, covering the ostium secundum in a flap-like fashion.
(the ostium primum fuses shut at some point)

Question 12

Is the foramen ovale the same thing as the ostium secundum?

Answer 12

Sort of. The foramen ovale is a combination of the ostium secundum and a hole in the septum secundum that allows blood to flow from the RA to LA.

Question 13

What’s the most common atrial septal defect (ASD)?

Answer 13

Persistence of the ostium secundum and/or incomplete formation of the septum secundum.

Patent foramen ovale is a subset of ostium secundum ASD.

Question 14

What often happens in ostium primum ASD?

Answer 14

There’s often a slit-like defect in the anterior leaflet of the mitral valve.

Question 15

What happens in sinus venosus AV defects?

Answer 15

Defect in formation of septum primum.

Often causes defect in a pulmonary vein such that it comes back to the RA.

Question 16

What’s a homeobox (hox) gene that seems to be particularly significant for causing congenital heart defects in humans?

Answer 16

Nkx2.5

Question 18

Why does ASD cause heart block?

Answer 18

People used to think it was due to the holes interfering with conduction…
but really it’s more about the impaired development of the specialize conduction cells.
(which can be caused by Nkx2.5 mutations)

Question 19

What are there, before there are great vessels?

Answer 19

5 pairs of symmetric aortic arches.

Question 20

Which aortic arch becomes the aorta?

Answer 20

The left 4th aortic arch.

Question 21

What cells give rise to the aortic arches?

Answer 21

Migrating neural crest cells.

Question 22

What if both left and right 4th aortic arches degenerate?

Answer 22

It’s a problem….

Question 23

3 organs affected by DeGeorge syndrome?
What, broadly, is the underlying cause?
(What, specifically, is the chromosomal abnormality?)

Answer 23

Heart (congen. defects), parathyroid, and thymus.
Neural crest cells don’t function properly.
Deletions on 22q11 cause DeGeorge.

Question 24

What seems to be the most important gene of 22q11 affected in DeGeorge syndrome?

Answer 24

TBX1

Question 25

What happens if the right 4th aortic arch gives rise to the aorta instead of the left 4th aortic arch?

Answer 25

This is called a right-sided aortic arch… which can be fine.
But, it can also cause an aortic ring that can compress the trachea.

Question 26

What is pulmonary atresia? How can it be survived without surgery, at least early on?

Answer 26

In pulmonary atresia, the PA doesn’t form. Blood can still get to the lungs via the ductus arteriosis… but when that obliterates, it’s a problem.

Question 27

What is dextrocardia?

Answer 27

The heart’s flipped, so it’s on the right….

Question 28

What is heterotaxy?

Answer 28

When there’s discordance in the L-R orientation between organs.

Question 29

What is thought very early to set up the L-R axis in the embryo?

Answer 29

Cilia that move morphogens in a predictable pattern.

Question 30

3 abnormalities in Kartagener’s syndrome?

What’s the underlying cause?

Answer 30

Infertility
Brochiectasis (airway damage)
Dextrocardia
-These are all caused by defects in cilia function.

Question 31

What “phenotypic switch” must happen in the cells that become valves?

Answer 31

Endothelial cells undergo epithelial to mesenchymal transformation (EMT), then migrate into “cardiac jelly” between endothelium and myocardium.
(forming endocardial “cushions”)

Question 32

What’s one signaling pathway involved in EMT?

Answer 32

Ras pathway. Defects in Ras signaling -> congenital heart defects involving valve formation.
(Recall: overactive Ras -> oncogenesis)

Question 33

What’s the difference between vasculogenesis and angiogenesis?

Answer 33

Vasculogensis: formation of vessels de novo from endothelial precurosis (angioblasts).
Angiogenesis: Formation of new blood vessels from pre-existing blood vessels.

Question 34

3 sets of signaling molecules involved in vascular development?

Answer 34

VEGF and VEGF receptors.
Notch ligands and receptors.
Semaphorin ligands and Plexin receptors.

Question 35

What’s interesting about the way Semaphorins guide vasculogenesis/angiogenesis?

Answer 35

Semaphorins are repulsive signals for axon guidance and blood vessel growth.

Question 36

What gives rise to the epicardium?

Answer 36

The proepicardial organ, from the septum transversum (which also gives rise to diaphragm and liver).

Question 37

What role does the epicardium play in heart development?

Answer 37

Epicardium induces myocardial maturation.

Question 38

What do neural crest cells have to do with the outflow tract?

Answer 38

Neural crest cells are necessary for the septation of the truncus arteriosis and cardiac outflow tract

Question 39

2 genes involved in neural crest migration?

Answer 39

Gata6

Sema3C