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Advanced Developmental > Cardiogenesis > Flashcards

Cardiogenesis Flashcards

1
Q

Approx how many deaths in the UK are due to cardiovascular disease?

A

1 in 4

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2
Q

How often does someone have a heart attack in the UK?

A

Every 3 minutes

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3
Q

What is congenital heart disease?

A

The rise of defects during development which can manifest much later in life
They cause about 800 deaths per year where a thirs are in babies under 1 year old

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4
Q

What is health care cost around cardiovascular disease in the UK?

A

£11 billion per year

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5
Q

How many genes does a drosophila have?

A

13,000

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6
Q

How many of the 929 human disease genes do flies have homologous genes?

A

548

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7
Q

What do cardiac cells arise from?

A

Ventral lateral mesoderm called the splanchnopleura

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8
Q

What are the two different heart fields?

A

1) The first lays down the scaffold of the heart but cells have a low proliferative capacity
2) The second heart field lies next to the first and develops temporarily behind the fist. Has a higher proliferative capacity so contributes to growth of the heart

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9
Q

When do angiogenic clusters form?

A

Immediately after gastrulation

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10
Q

Where are angiogenic clusters formed from?

A

The ventral aspect of the lateral mesoderm

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11
Q

What does Dpp stand for?

A

decapentaplegic

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12
Q

Why does the corresponding between the dropsophila and vertebrate heart development eventually stop?

A

Because the drosophila heart does not show any looping or has any chambers

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13
Q

What is tinman?

A

Essential for heart formation in the drosophila

Transcription factor of homeobox

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14
Q

Where is tinman expressed?

A

Initially it is expressed throughout the embryo but is later restricted to the dorsal vessel
Later on it is restricted to the heart tube

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15
Q

What happens in a tinman mutant?

A

Failure to form the heart tube = no heart

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16
Q

What are the vertebrate homologues of tinman?

A

Belong to the Nk-2 family of homeobox transcription factors

eg Nk2.5

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17
Q

Where is Nk2.5 expressed?

A

In the cardiac crescent

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18
Q

Nk2.5 mice mutants show what?

A

Formation of a heart but it has cardiac defects at the looping stage

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19
Q

What induces Nk2.5 expression?

A

BMP signalling

20
Q

How can you test if BMP induces Nk2.5?

A

Use a gain of function approach

eg soak a bead in BMP to induce ectopic expression

21
Q

Where must a BMP soaked bead be placed in an embryo and why?

A

It must be placed in anterior mesoderm or anterior notochord

Posterior notochord secretes BMP inhibitors eg chordin which would block the effect of the bead

22
Q

What is secreted in the anterior mesoderm to stop BMPs from being inhibited?

A

Wnt inhibitors eg serberus

These stop negative activity of Wnt pn BMP signalling

23
Q

What are the steps involved in the formation of the heart tube?

A

1) 2 bilateral tubes form
2) Thickening of mesoderm round the tubes
3) Ventral migration occurs so cells come together in a ventral position
4) The tubes fuse and form a single endocardial tube surrounded by epimyocardium

24
Q

What is epimyocardium?

A

Contains the precursor cells for the cardiac muscles

25
Q

What is endocardium?

A

Contains the precursors of the endothelial lining of the heart and cushion cells that form valves

26
Q

What does myocardium contain?

A

Myocytes of atria and ventricles

Purkinje fibres

27
Q

What is induced by tinman?

A

Dmef2 (fly gene)

28
Q

What is the vertebrate homologue of Dmef2?

A

Mef2A, B and C

29
Q

Which of the Dmef2 homologues is expressed earliest in the heart?

A

Mef2c

30
Q

Mef2c mutant shows what?

A

No heart looping and no right ventricule forms

Upregulation of Mef2B

31
Q

Which genes are involved in the formation of the heart tube in vertebrates and drosophila?

A 
V = GATA
D = pannier
32
Q

GATA 1-3 are involved in what process?

A

Hematopoesis

33
Q

GATA 4-6 are involved in what process?

A

Cardiogenesis

GATA 4 is expressed earlies

34
Q

What does a GATA 4 mouse mutant show?

A

Failure to form the heart tube
2 tubes remain in their lateral position
This is called cardiac bifida

35
Q

Which direction does the heart loop?

A

To the right

36
Q

What are the suggested mechanisms that explain why the heart loops to a particular direction?

A

a) Asymetric division
b) Asymetric cell death
c) changes in cell shape triggered by asymetric distribution of microtubules and actin bundles

37
Q

What are lefty and nodal and where are they expressed?

A

TGFb related molecules

Expressed on the left of the embryo

38
Q

When is the first asymetry established?

A

When signalling through activin receptor IIa inhibits Shh expression on the right side of the embryo

39
Q

What does iv stand for?

A

Inversus viscerum

40
Q

What does iv encode for?

A

A dynein - protein involved in the movement of cilia

41
Q

What does inv stand for?

A

Inversion of embyonic turning - encodes for inversin, a protein containing ankyrin repeats found in cilia

42
Q

Describe the proposed model that establishes and maintains asymetry

A

Inv and Iv are required for cilia movement and rotation

Cilia rotation establishes a preferential flow of Nodal and Lefty molecules to the left side of the embryo

43
Q

What are dHand and Ehand?

A

bHLH transcription factors with specific expression in the left and right ventricles

44
Q

What happens in dHand mutant mice?

A

They die at E10.5 and have right ventricle hypoplasia

45
Q

What happens in eHand mutant mice?

A

Mice die at E8.5 with placental defects

46
Q

What happens if mice have a conditional eHand mutation?

A

The mice survive until birth but they have a left vetricle defect

Advanced Developmental (25 decks)

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