L17 - Development of the Heart

Question 1

Leading cause of death worldwide

Answer 1

CVD

Question 2

How many poeple in the UK died from CVD in the UK last year

Answer 2

152000

Question 3

What is a congenital heart defect

Answer 3

A strucutral malformation of the heart which has arisen due to inappropriate development

Question 4

Describe the heart structure of higher order vertebrates

Answer 4

4 chambers
2 atria 2 ventricles - to allow oxygenated and deoxygenated blood to be kept separate in the heart
2 different circulatory systems

Question 5

Describe the heart structure of Xenopus

Answer 5

3 chambers

2 atria with the single ventricle - ox and deoxy blood are still kept separate

Question 6

Describe the heat strucutre of zebrafish

Answer 6

2 chambered heart

Single atria and ventricle

Question 7

Describe the heart of drosophila

Answer 7

Tubular heart

Single tube lined with valves to promote the unidirectional flow of blood - this is the simplest

Question 8

Key processs in the morphological development of the heart

Answer 8

Cardiac mesoderm forms the cardiac cresent
Cells within the crescent migrate toward the midline to form a single tube
Once formed - asymmetric process of heart looping takes place
Maturation

Question 9

Discuss how cardiac precurrosors are foudn

Answer 9

As a bilateral (2) populations of cells around the midline

Question 10

Describethe formation of the heart tube

Answer 10

Cells migrate to the midline and fuse forming the heart tube

Question 11

Describe heart looping

Answer 11

Heart tube undergoes asymmetric bending morphogenesis termed heart looping

Question 12

What is maturation of the heart

Answer 12

THe formation of structures which are required for prooper fucntion
E.g. septa, trabeculae, valves etc.

Question 13

What are the two population of cardiac precurrsors known as

Answer 13

First heart field cells

Second heart field cells

Question 14

What do theFHF give rise to

Answer 14

Left ventricle, left atria, right atria

Question 15

What doe the SHF cells give rise to

Answer 15

Right ventricle, left atria, right atria and outflow tract

Question 16

Describe where cardiac cells are specified in FISH and in MOUSE

Answer 16

MOUSE - primitive streak

FISH - embryonic margin

Question 17

What signalling is required for specification of the cardiac mesoderm

Answer 17

Non canonical Wnt signalling

Question 18

What is required for specification of FHF cells

Answer 18

BMP

Question 19

What is required for specification of the SHF cells

Answer 19

B-catenin / FGF

Question 20

Once specified describe the migration of the FHF and SHF cells

Answer 20

FHF form the primitive heart tube

SHF in the adjacent mesoderm

Question 21

The two heart field progenitors express

Answer 21

Different sets of factors

Question 22

Both FHF and SHF express

Answer 22

Nkx2.5

Question 23

Describe what happens where there is no Nkx2.5 present

Answer 23

Lack of primary myocytes in the heart

Question 24

Describe the different heart pattenring events which lead to functional regionalisation

Answer 24

Chamber vs. non chamber
Atrial vs. ventricular contractility
Inflow, atrioventricular canal, outflow

Question 25

Fucntional regionalisation of the heart is a complex

Answer 25

Interplay between activating and inhibitory factors

Question 26

Notch - Tbx20 required for

Answer 26

Chamber myocardium

Question 27

Nppa and nppb are markers of

Answer 27

Chamber myocaridium

Question 28

BMP - TBx2 required for

Answer 28

Atrioventriuclar canal (AVC)

Question 29

Describe the effect of Tbx2 mutant mice

Answer 29

Abnormal valve morphology | Abronormal Nppa expression (marker of chamber)

Question 30

What is tbx20 requires for What are the effects of tbx20 KOs

Answer 30

Required for the formation of chambers Loss of expression of the chamber gene Massive upregulation of Tbx2 throughout the heart

Question 31

Tbx2 is a

Answer 31

Valve marker

Question 32

Describe the interaction between Tbx20 and Tbx2

Answer 32

Tbx20 represses Tbx2

Question 33

Describe what processes are involved in heart looping morphogenesis

Answer 33

Changes in cell shape Growth of the heart tube Asymmetric cell movements at the poles of the hearts Regional changes in ECM Lateralised cell signalling in the embryo

Question 34

During heart looping morphogenesis what happens to the cells on the inner cruvature

Answer 34

Stay cubioidal

Question 35

During heart looping morphogenesis what happens to the cells on the outer cruvature

Answer 35

Grow more and elongates causing a change in the orientation

Question 36

What is myl7

Answer 36

Cardiac marker

Question 37

Describe the growth of the heart tube

Answer 37

Initially made up of FHF cells surrounded by SHF cells | SHF add in at either pole

Question 38

what does a Lac7 reported show regarding the lineage of cells that expressed islet 1

Answer 38

End up in the hart itself

Question 39

Where is islet1 usually expressed

Answer 39

In the mesoderm adjacent to the heart

Question 40

Describe what is seen in an insitu analysis of myl7 for Islet 1 mutant mice

Answer 40

Heart is reduced in size and looping is incorrect

Question 41

What two conditions can be causes by L/R symmetry abnormalities Which of theses is usually asymptomatic, which one is associated with signifcatnt pathology

Answer 41

Situs inversus - usually asymptomatic Situs abmbiguous/heterotaxia - usually associated with significant pathology

Question 42

What is associated with heterotaxia

Answer 42

Congenital heart defects

Question 43

Where is nodal expressed prior to the formation of the organs

Answer 43

Left lateral plate mesoderm

Question 44

Loss of nodal leads to

Answer 44

Disrupted organ symmetry

Question 45

What is the ZF homolgue of nodal

Answer 45

spaw

Question 46

Describe the role of the node in the asymetric expression of Spaw (nodal)

Answer 46

Node is a transient cup shaped organ with cilia which beat in a clockwise direction This creates a directional fluid flow Results in elevated Ca on the left side of the embryo Results in increased Spaw on the left hand side of the embryo

Question 47

What happens once Nodal reaches the more anterior regions of the embryo

Answer 47

Asymm expression of genes which are localisaed to specific organs

Question 48

Describe the process/role of asymmetry in the development of the heart

Answer 48

asymmetric gene expression in the organ anlage nodal target genes expressed in the left half of the cardiac disc Asymmetric movement of the cells to form the heart tube Cardiac disc undergoes rotation and involution to form a tube

Question 49

Describe the effects of randomisation of lateralised gene expression in fish

Answer 49

Disruption to KV form or function results in randomisation of Spaw and directional heart dipalcemrnt

Question 50

Describe the effects of randomisation of lateralised gene expression in humans

Answer 50

Individuals with mutations in cilary genes which cause primary cilary dyskinesia and also exhibit heterotaxia

Question 51

What occurs when there is an absence of lateralised gene expression in Fish

Answer 51

Leads to failure of the leftward displacement of the heart tube

Question 52

During heart development the heart is

Answer 52

Functional

Question 53

What are the two forces acting in heart development

Answer 53

Cardiac contractility - one source of mechanical force in the dev. heart Cardiac function causes blood to flow through the heart as it is developing

Question 54

What is blood flow improtant for

Answer 54

Spatiotemporal gene expression of forming valves Occurs through flow response genes Required for maturation

Question 55

Give an example of a flow response gene

Answer 55

Klf2

Question 56

Describe what happens when the heart relaxes What is the effect of this

Answer 56

Some retrograde flow through narrowins Sensed by cells in adjacent regions Genes which are required for valve formation are turned on