Cardiogenesis

Question 1

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

Answer 1

1 in 4

Question 2

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

Answer 2

Every 3 minutes

Question 3

What is congenital heart disease?

Answer 3

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

Question 4

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

Answer 4

£11 billion per year

Question 5

How many genes does a drosophila have?

Answer 5

13,000

Question 6

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

Answer 6

548

Question 7

What do cardiac cells arise from?

Answer 7

Ventral lateral mesoderm called the splanchnopleura

Question 8

What are the two different heart fields?

Answer 8

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

Question 9

When do angiogenic clusters form?

Answer 9

Immediately after gastrulation

Question 10

Where are angiogenic clusters formed from?

Answer 10

The ventral aspect of the lateral mesoderm

Question 11

What does Dpp stand for?

Answer 11

decapentaplegic

Question 12

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

Answer 12

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

Question 13

What is tinman?

Answer 13

Essential for heart formation in the drosophila

Transcription factor of homeobox

Question 14

Where is tinman expressed?

Answer 14

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

Question 15

What happens in a tinman mutant?

Answer 15

Failure to form the heart tube = no heart

Question 16

What are the vertebrate homologues of tinman?

Answer 16

Belong to the Nk-2 family of homeobox transcription factors

eg Nk2.5

Question 17

Where is Nk2.5 expressed?

Answer 17

In the cardiac crescent

Question 18

Nk2.5 mice mutants show what?

Answer 18

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

Question 19

What induces Nk2.5 expression?

Answer 19

BMP signalling

Question 20

How can you test if BMP induces Nk2.5?

Answer 20

Use a gain of function approach

eg soak a bead in BMP to induce ectopic expression

Question 21

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

Answer 21

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

Question 22

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

Answer 22

Wnt inhibitors eg serberus

These stop negative activity of Wnt pn BMP signalling

Question 23

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

Answer 23

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

Question 24

What is epimyocardium?

Answer 24

Contains the precursor cells for the cardiac muscles

Question 25

What is endocardium?

Answer 25

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

Question 26

What does myocardium contain?

Answer 26

Myocytes of atria and ventricles | Purkinje fibres

Question 27

What is induced by tinman?

Answer 27

Dmef2 (fly gene)

Question 28

What is the vertebrate homologue of Dmef2?

Answer 28

Mef2A, B and C

Question 29

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

Answer 29

Mef2c

Question 30

Mef2c mutant shows what?

Answer 30

No heart looping and no right ventricule forms | Upregulation of Mef2B

Question 31

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

Answer 31

``` V = GATA D = pannier ```

Question 32

GATA 1-3 are involved in what process?

Answer 32

Hematopoesis

Question 33

GATA 4-6 are involved in what process?

Answer 33

Cardiogenesis | GATA 4 is expressed earlies

Question 34

What does a GATA 4 mouse mutant show?

Answer 34

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

Question 35

Which direction does the heart loop?

Answer 35

To the right

Question 36

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

Answer 36

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

Question 37

What are lefty and nodal and where are they expressed?

Answer 37

TGFb related molecules | Expressed on the left of the embryo

Question 38

When is the first asymetry established?

Answer 38

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

Question 39

What does iv stand for?

Answer 39

Inversus viscerum

Question 40

What does iv encode for?

Answer 40

A dynein - protein involved in the movement of cilia

Question 41

What does inv stand for?

Answer 41

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

Question 42

Describe the proposed model that establishes and maintains asymetry

Answer 42

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

Question 43

What are dHand and Ehand?

Answer 43

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

Question 44

What happens in dHand mutant mice?

Answer 44

They die at E10.5 and have right ventricle hypoplasia

Question 45

What happens in eHand mutant mice?

Answer 45

Mice die at E8.5 with placental defects

Question 46

What happens if mice have a conditional eHand mutation?

Answer 46

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