Case 11 - Heart development ... to be finished after birth?!
Learning goals
1. How does the heart develop?
a. Anatomy.
2. Adaptations after birth.
a. Umbilical cord circulation + start of circulation through lungs.
3. What can go wrong?
a. Focus on TOF.
b. Why does it go wrong?
Mutation: additional cut in the wild type.
Embryonic Heart development - stages
1. Heart tube formation (week 3)
2. Heart looping (week 4)
3. Ballooning → heart chamber formation (week 5)
4. Heart septation / valve development (week 6 + 7)
It starts beating on day 22 and pumping blood on day 24/25.
NOTE→This means that the heart develops while pumping blood.
Cardiac cells
● Wnt-antagonist in the anterior endoderm inhibits Wnt-
signaling and induces cell differentiation in the overlying
mesoderm (lang en breed gradient).
● Cardiac progenitor cells migrate from the
intraembryonic mesoderm through the primitive streak in
the cranial-lateral direction.
● In the lateral plate mesoderm (splanchnic subdivision)
they form the cardiac crescent on both sides of the
embryo ( → primary heart field).
It all starts when cardiac progenitor cells migrate during early
gastrulation from the intraembryonic mesoderm at the cranial third of the primitive streak.
They migrate cranial-lateral to both sides of the primitive streak.
➔ The factors Mesp1 and Mesp2 are expressed during this stage and are necessary
for migration of these cells.
Eventually, the cardiac progenitor cells migrate into the lateral plate mesoderm, which
extends to the developing head fold where it forms a cardiac crescent.
, - The lateral plate mesoderm is subdivided into two. The cardiac crescent forms out of
the splanchnic mesodermal subdivision.
Formation of the primitive heart tube
● Cranial most portion of the cardiac crest
swings ventral/caudal.
( → lies ventral to developing foregut
endoderm).
● Right and left side fuse together (cranial-
to-caudal progression).
● Endocardial tubes (vascular elements)
develop on both sides.
➢ Vasculogenesis is driven by
vascular endothelial growth factor
(Vegf) → come from cranial endoderm.
● Both tubes fuse and form primitive heart tube.
● Late 3rd week: cranial folding brings primitive heart tube into the thoracic region.
➔ Endocardial tube consists of endothelium surrounded by splanchnic
mesoderm (myocytic progenitors will form the myocardium / heart muscle).
Primitive heart tube
- Endocardial (endothelium) tube surrounded by
cardiac jelly (layer of extracellular matrix) within
myocardial tube.
- Splanchnic mesoderm that contains cardiomyocytic
progenitors → they will invest to form the
myocardium.
➔ Tube will lengthen, due to the 2nd migration wave of
cells.
● Caudal end: sinus venosus or inflow tract.
● Cranial end: bulbus cordis or outflow tract
● Primitive atrium ( → right & left atrium) and primitive
ventricle ( → left ventricle) are separated by
atrioventricular sulcus.
● Primitive ventricle is separated from the bulbus
cordis ( → right ventricle) by the bulboventricular
sulcus.
, THEN (week 4) →The primitive heart tube is taken into the pericardial
cavity that is still developing. This is done by the dorsal mesocardium
(dorsal mesentery of the heart).
HOWEVER→suddenly it tears apart and the heart is in the pericardial
cavity where it stays in place because of the attached vasculature. The
torn part then forms the transverse pericardial sinus in the pericardial
sac. This space will separate the cardiac inflow and outflow from each
other.
HOWEVER→Not all the cells in the adult heart come from the primitive heart field. Also some
precursor cardiogenic cells come from the mesoderm that lies next to the initial cardiac
crescent.
So, besides the proliferation of the primitive heart tube, also recruitment of those cardiac
progenitor cells is done. This second place is called the secondary heart field. Cells from
here are especially used for the lengthening of the primitive heart tube at the most cranial
end, where the outflow tract lies.
NOTE→Probably, the right ventricle is mostly made from cells out of the secondary heart
field.
Cardiac looping
Learning goals
1. How does the heart develop?
a. Anatomy.
2. Adaptations after birth.
a. Umbilical cord circulation + start of circulation through lungs.
3. What can go wrong?
a. Focus on TOF.
b. Why does it go wrong?
Mutation: additional cut in the wild type.
Embryonic Heart development - stages
1. Heart tube formation (week 3)
2. Heart looping (week 4)
3. Ballooning → heart chamber formation (week 5)
4. Heart septation / valve development (week 6 + 7)
It starts beating on day 22 and pumping blood on day 24/25.
NOTE→This means that the heart develops while pumping blood.
Cardiac cells
● Wnt-antagonist in the anterior endoderm inhibits Wnt-
signaling and induces cell differentiation in the overlying
mesoderm (lang en breed gradient).
● Cardiac progenitor cells migrate from the
intraembryonic mesoderm through the primitive streak in
the cranial-lateral direction.
● In the lateral plate mesoderm (splanchnic subdivision)
they form the cardiac crescent on both sides of the
embryo ( → primary heart field).
It all starts when cardiac progenitor cells migrate during early
gastrulation from the intraembryonic mesoderm at the cranial third of the primitive streak.
They migrate cranial-lateral to both sides of the primitive streak.
➔ The factors Mesp1 and Mesp2 are expressed during this stage and are necessary
for migration of these cells.
Eventually, the cardiac progenitor cells migrate into the lateral plate mesoderm, which
extends to the developing head fold where it forms a cardiac crescent.
, - The lateral plate mesoderm is subdivided into two. The cardiac crescent forms out of
the splanchnic mesodermal subdivision.
Formation of the primitive heart tube
● Cranial most portion of the cardiac crest
swings ventral/caudal.
( → lies ventral to developing foregut
endoderm).
● Right and left side fuse together (cranial-
to-caudal progression).
● Endocardial tubes (vascular elements)
develop on both sides.
➢ Vasculogenesis is driven by
vascular endothelial growth factor
(Vegf) → come from cranial endoderm.
● Both tubes fuse and form primitive heart tube.
● Late 3rd week: cranial folding brings primitive heart tube into the thoracic region.
➔ Endocardial tube consists of endothelium surrounded by splanchnic
mesoderm (myocytic progenitors will form the myocardium / heart muscle).
Primitive heart tube
- Endocardial (endothelium) tube surrounded by
cardiac jelly (layer of extracellular matrix) within
myocardial tube.
- Splanchnic mesoderm that contains cardiomyocytic
progenitors → they will invest to form the
myocardium.
➔ Tube will lengthen, due to the 2nd migration wave of
cells.
● Caudal end: sinus venosus or inflow tract.
● Cranial end: bulbus cordis or outflow tract
● Primitive atrium ( → right & left atrium) and primitive
ventricle ( → left ventricle) are separated by
atrioventricular sulcus.
● Primitive ventricle is separated from the bulbus
cordis ( → right ventricle) by the bulboventricular
sulcus.
, THEN (week 4) →The primitive heart tube is taken into the pericardial
cavity that is still developing. This is done by the dorsal mesocardium
(dorsal mesentery of the heart).
HOWEVER→suddenly it tears apart and the heart is in the pericardial
cavity where it stays in place because of the attached vasculature. The
torn part then forms the transverse pericardial sinus in the pericardial
sac. This space will separate the cardiac inflow and outflow from each
other.
HOWEVER→Not all the cells in the adult heart come from the primitive heart field. Also some
precursor cardiogenic cells come from the mesoderm that lies next to the initial cardiac
crescent.
So, besides the proliferation of the primitive heart tube, also recruitment of those cardiac
progenitor cells is done. This second place is called the secondary heart field. Cells from
here are especially used for the lengthening of the primitive heart tube at the most cranial
end, where the outflow tract lies.
NOTE→Probably, the right ventricle is mostly made from cells out of the secondary heart
field.
Cardiac looping
