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BMS242 Developmental Biology > L17 - Development of the Heart > Flashcards

L17 - Development of the Heart Flashcards

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1
Q

Leading cause of death worldwide

A

CVD

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2
Q

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

A

152000

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3
Q

What is a congenital heart defect

A

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

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4
Q

Describe the heart structure of higher order vertebrates

A

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

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5
Q

Describe the heart structure of Xenopus

A

3 chambers

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

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6
Q

Describe the heat strucutre of zebrafish

A

2 chambered heart

Single atria and ventricle

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7
Q

Describe the heart of drosophila

A

Tubular heart

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

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8
Q

Key processs in the morphological development of the heart

A

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

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9
Q

Discuss how cardiac precurrosors are foudn

A

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

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10
Q

Describethe formation of the heart tube

A

Cells migrate to the midline and fuse forming the heart tube

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11
Q

Describe heart looping

A

Heart tube undergoes asymmetric bending morphogenesis termed heart looping

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12
Q

What is maturation of the heart

A

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

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13
Q

What are the two population of cardiac precurrsors known as

A

First heart field cells

Second heart field cells

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14
Q

What do theFHF give rise to

A

Left ventricle, left atria, right atria

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15
Q

What doe the SHF cells give rise to

A

Right ventricle, left atria, right atria and outflow tract

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16
Q

Describe where cardiac cells are specified in FISH and in MOUSE

A

MOUSE - primitive streak

FISH - embryonic margin

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17
Q

What signalling is required for specification of the cardiac mesoderm

A

Non canonical Wnt signalling

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18
Q

What is required for specification of FHF cells

A

BMP

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19
Q

What is required for specification of the SHF cells

A

B-catenin / FGF

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20
Q

Once specified describe the migration of the FHF and SHF cells

A

FHF form the primitive heart tube

SHF in the adjacent mesoderm

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21
Q

The two heart field progenitors express

A

Different sets of factors

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22
Q

Both FHF and SHF express

A

Nkx2.5

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23
Q

Describe what happens where there is no Nkx2.5 present

A

Lack of primary myocytes in the heart

24
Q

Describe the different heart pattenring events which lead to functional regionalisation

A

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

25
Q

Fucntional regionalisation of the heart is a complex

A

Interplay between activating and inhibitory factors

26
Q

Notch - Tbx20 required for

A

Chamber myocardium

27
Q

Nppa and nppb are markers of

A

Chamber myocaridium

28
Q

BMP - TBx2 required for

A

Atrioventriuclar canal (AVC)

29
Q

Describe the effect of Tbx2 mutant mice

A

Abnormal valve morphology

Abronormal Nppa expression (marker of chamber)

30
Q

What is tbx20 requires for

What are the effects of tbx20 KOs

A

Required for the formation of chambers
Loss of expression of the chamber gene

Massive upregulation of Tbx2 throughout the heart

31
Q

Tbx2 is a

A

Valve marker

32
Q

Describe the interaction between Tbx20 and Tbx2

A

Tbx20 represses Tbx2

33
Q

Describe what processes are involved in heart looping morphogenesis

A

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

34
Q

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

A

Stay cubioidal

35
Q

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

A

Grow more and elongates causing a change in the orientation

36
Q

What is myl7

A

Cardiac marker

37
Q

Describe the growth of the heart tube

A

Initially made up of FHF cells surrounded by SHF cells

SHF add in at either pole

38
Q

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

A

End up in the hart itself

39
Q

Where is islet1 usually expressed

A

In the mesoderm adjacent to the heart

40
Q

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

A

Heart is reduced in size and looping is incorrect

41
Q

What two conditions can be causes by L/R symmetry abnormalities

Which of theses is usually asymptomatic, which one is associated with signifcatnt pathology

A

Situs inversus - usually asymptomatic

Situs abmbiguous/heterotaxia - usually associated with significant pathology

42
Q

What is associated with heterotaxia

A

Congenital heart defects

43
Q

Where is nodal expressed prior to the formation of the organs

A

Left lateral plate mesoderm

44
Q

Loss of nodal leads to

A

Disrupted organ symmetry

45
Q

What is the ZF homolgue of nodal

A

spaw

46
Q

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

A

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

47
Q

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

A

Asymm expression of genes which are localisaed to specific organs

48
Q

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

A

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

49
Q

Describe the effects of randomisation of lateralised gene expression in fish

A

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

50
Q

Describe the effects of randomisation of lateralised gene expression in humans

A

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

51
Q

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

A

Leads to failure of the leftward displacement of the heart tube

52
Q

During heart development the heart is

A

Functional

53
Q

What are the two forces acting in heart development

A

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

54
Q

What is blood flow improtant for

A

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

55
Q

Give an example of a flow response gene

A

Klf2

56
Q

Describe what happens when the heart relaxes

What is the effect of this

A

Some retrograde flow through narrowins

Sensed by cells in adjacent regions

Genes which are required for valve formation are turned on

BMS242 Developmental Biology (17 decks)

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