Embryology

Question 1

Descriptive

Answer 1

Repeated observation of post mortem species to determine stages of development.

Question 2

Mechanistic

Answer 2

Experimentation to determine roles of genes/proteins/environment factors in cardiac development.

Question 3

Gastrulation

Answer 3

Mass movement and invagination of the blastula to form three layers - ectoderm, mesoderm and endoderm.

Question 4

Ectoderm

Answer 4

Outside layer - skin, nervous, system, neural crest (contributes to cardiac outflow, coronary arteries).

Question 5

Mesoderm

Answer 5

Middle - all types of muscle, most system, kidneys, blood, bone.

Question 6

Endoderm

Answer 6

Inside - gastrointestinal tract - liver, pancreas, endocrine organs - NOT SMOOTH MUSCLE.

Question 7

CV embryology

Answer 7

Most of the CVS is from cells from the mesoderm and from the neural crest cells in the ectoderm.

Question 8

Heart fields

Answer 8

First heart field - smaller and less curved down.
Second heart field - curved downwards.
FHF - future left ventricle.
SHF - outflow tract, future right ventricle, atria.
The FHF creates a scaffold which is added to by the SHF and cardiac neural crest.

Question 9

Cardiac transcription factors

Answer 9

Expressed in a tissue specific manner.
Nkx2.5
GATA
Hand
Tbx
MEF2
Pitx2
Fog-1

Question 10

Stages of cardiac formation

Answer 10

1) Formation of the primitive heart tube.
2) Cardiac looping.
3) Cardiac septation.

Question 11

Formation of the primitive heart tube

Answer 11

WATCH VIDEO
Stage 1
Overexpression of Nkx.2.5 (by injecting RNA) - increases heart size.
Preventing GATA4 transcription - induces cardia bifida - failure of the endocardial tubes to fuse.

Question 12

Cardiac looping

Answer 12

WATCH VIDEO
Stage 2
Vertebrate hearts have a leftward ventricle.
Many mutations are associated with improper left-right positioning.
The node secretes nodal - circulates to the left due to ciliary movement.
A cascade of TFs (e.g. Lefty, Pitx2, Fog-1) transduce looping.
If you prevent Fog-1 transcription - prevents cardiac looping.

Question 13

Cardiac Septation

Answer 13

WATCH VIDEO
Stage 3
Endocardial cushion formation.
Mutations in TF can cause some human congenital cardiac defects.

Question 14

Why do we need circulation?

Answer 14

Every cell needs to be bathed in fluid and within 2mm from oxygen.
Reproduces the extracellular environment of primitive uni and multicellular organisms in the primeval ocean.

Question 15

Distribution of total blood volume in the circulatory system

Answer 15

64% - veins.
9% - lungs.
8% - small arteries and arterioles.
7% - heart.
7% - large arteries.
5% - capillaries.

Question 16

Arterial system

Answer 16

Elastic arteries - major distribution vessels - aorta, carotids, subclavian, pulmonary - increase efficiency.
Muscular arteries - control distribution.
Arterioles - terminal branches - <300 microns diameter.

Question 17

Capillaries

Answer 17

Blood flow regulated by precapillary sphincters.
3-40 microns in diameter.
Three types:
- continuous (most common)
- fenestrated (kidney, small intestine, endocrine glands)
- discontinuous (liver sinusoids)

Question 18

Venous system

Answer 18

Return blood to the heart.
Valves allow muscular pumping.
Some peristaltic movement.

Question 19

Structure of artery/vein

Answer 19

Endothelium (intima), basement membrane, vascular smooth muscle cells (media), internal elastic lamina, fibroblast (adventitia), external elastic lamina.

Question 20

Embryology of the circulation - days

Answer 20

Day 17 - formation of blood islands - in extraembryonic mesoderm - core of hemoblasts surrounded by endothelial cells.
Day 17-21 - vascularization of the yolk sac, chorionic villus and stalk.
Day 18 - vasculogenesis commences - angioblasts (from splanchnopleuric mesoderm) coalesce to form angioblastic cords throughout the embryonic disc.
Day 18 onwards - vasculogenesis is added to by angiogenesis - driven by angiogenic growth factors and takes place by proliferation and sprouting. Other mesodermal cells are recruited.

Question 21

What drives embryonic vessel development?

Answer 21

Angiogenic growth factors - vascular endothelial growth factor, angiopoietin 1 and 2.
Repulsive signals - plexin/semaphorin signalling, ephrin/Eph interactions.

Question 22

1st and 2nd aortic arches

Answer 22

Become minor head vessels.
1st - small part of maxillary.
2nd - artery to stapedius.

Question 23

3rd aortic arches

Answer 23

Portion between 3rd and 4th arch disappears - becomes common carotid arteries and proximal internal carotid arteries.
Distal internal carotids come from extension of dorsal aortae.

Question 24

Right dorsal aorta and right 4th aortic arch

Answer 24

R dorsal aorta looses connections with midline aorta and 6th arch - still connected to R 4th arch.
Acquires branch 7th cervical intersegmental artery - grows into R upper limb.
Right subclavian artery - derived from R 4th arch, right dorsal aorta and 7th intersegmental artery.

Question 25

Left dorsal aorta and left 4th aortic arch

Answer 25

Left dorsal aorta continues into trunk.
Left 7th cervical intersegmental artery - grows into left subclavian artery.
Right subclavian artery - derived from right 4th arch, right dorsal aorta and right 7th intersegmental artery.
NO 5th ARCHES

Question 26

6th aortic arches

Answer 26

Rich arch may form part of the pulmonary trunk.
Left arch forms ductus arteriosus - communication between pulmonary artery and aorta.