cardiogenesis Flashcards

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1
Q

what is congenital heart disease?

A

structural malformations of the heart occurring because the heart has not gone through normal development

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2
Q

what does the 1st heart field give rise to?

A

heart tube —–> left ventricle, left and right atria

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3
Q

what does the 2nd heart field give rise to?

A

cells adding to heart tube —–> right ventricle, left + right atria and outflow tract

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4
Q

what transcription factors are expressed in the first heart field cells?

A

tbx5

nkx2.5

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5
Q

what transcription factors are expressed in the second heart field cells?

A

nkx2.5

islet1

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6
Q

which genetic pathway is involved in specifying chamber myocardium? describe it.

A

notch-tbx20 pathway

  1. notch activates many genes
  2. tbx20 activated
  3. tbx20 inhibits tbx2 and bmp2
  4. tbx20 activates nppa & nppb
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7
Q

which genetic pathway is involved in specifying the atrioventricular canal? describe it.

A

bmp2-tbx2 pathway

1. bmp2 upstream of tbx2

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8
Q

what are some markers of chamber myocardium?

A

Nppa

Nppb

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9
Q

DEFINE: heterotaxia

A

abnormalities in left/right asymmetry

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10
Q

Situs invertus

A

complete reversal of left/right organisation of organs

asymptomatic

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11
Q

Situs ambiguous = heterotaxia

A

disrupted left-right asymmetry of organs + not a full reversal
abnormal cardiac development + function
congenital heart defects

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12
Q

how does nodal regulate organ asymmetry?

A
  1. node forms during early somitogenesis. node is lined with motile cilia –> creates directional fluid flow in the node
  2. pushes fluid to left side of node
  3. elevated extracellular Ca2+ levels in left side of node
  4. nodal expression turned on in left lateral plate mesoderm
  5. nodal turns on its own expression as it propagates anteriorly in left lateral plate mesoderm
  6. nodal turns on asymmetric gene expression in organ anlage
    - turns on cyclops and lefty2
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13
Q

what is primary ciliary dyskinesia

A

immotile cilia caused by mutations in ciliary genes

can also cause heterotaxia

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14
Q

how do valves form?

A

retrograde blood flow detected by adjoining cells —> turns on flow-responsive genes e.g. klf2

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15
Q

in humans, when is the heart well formed by?

A

7 weeks

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16
Q

cardiac specification

A
  1. non-canonical wnt signalling pathway specifies 1st heart field cells or 2nd heart field cells
  2. bmp signalling pathway specifies 1st heart field cells
    canonical wnt signalling pathway specifies 2nd heart field cells
17
Q

what are the changes in cell shape occurring as the heart undergoes looping?

A

cells in inner curvature of ventricle remain cuboidal

cells in outer curvature of ventricle grow and elongate + change their orientation

18
Q

what is the zebrafish Nodal homolog?

A

spaw

19
Q

which genes are expressed in the left heart field?

A

cyclops

lefty2

20
Q

what are the two sources of mechanical force in the developing heart?

A
  • cardiac contractibility

- blood flow creating stress on walls of heart tube