cardiogenesis Flashcards
what is congenital heart disease?
structural malformations of the heart occurring because the heart has not gone through normal development
what does the 1st heart field give rise to?
heart tube —–> left ventricle, left and right atria
what does the 2nd heart field give rise to?
cells adding to heart tube —–> right ventricle, left + right atria and outflow tract
what transcription factors are expressed in the first heart field cells?
tbx5
nkx2.5
what transcription factors are expressed in the second heart field cells?
nkx2.5
islet1
which genetic pathway is involved in specifying chamber myocardium? describe it.
notch-tbx20 pathway
- notch activates many genes
- tbx20 activated
- tbx20 inhibits tbx2 and bmp2
- tbx20 activates nppa & nppb
which genetic pathway is involved in specifying the atrioventricular canal? describe it.
bmp2-tbx2 pathway
1. bmp2 upstream of tbx2
what are some markers of chamber myocardium?
Nppa
Nppb
DEFINE: heterotaxia
abnormalities in left/right asymmetry
Situs invertus
complete reversal of left/right organisation of organs
asymptomatic
Situs ambiguous = heterotaxia
disrupted left-right asymmetry of organs + not a full reversal
abnormal cardiac development + function
congenital heart defects
how does nodal regulate organ asymmetry?
- node forms during early somitogenesis. node is lined with motile cilia –> creates directional fluid flow in the node
- pushes fluid to left side of node
- elevated extracellular Ca2+ levels in left side of node
- nodal expression turned on in left lateral plate mesoderm
- nodal turns on its own expression as it propagates anteriorly in left lateral plate mesoderm
- nodal turns on asymmetric gene expression in organ anlage
- turns on cyclops and lefty2
what is primary ciliary dyskinesia
immotile cilia caused by mutations in ciliary genes
can also cause heterotaxia
how do valves form?
retrograde blood flow detected by adjoining cells —> turns on flow-responsive genes e.g. klf2
in humans, when is the heart well formed by?
7 weeks