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BMS242 Developmental Biology > L11 - Mesoderm Patterning and Somite Formation > Flashcards

L11 - Mesoderm Patterning and Somite Formation Flashcards

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1
Q

What are the four mesodermal tissues

A

Axial mesoderm
Paraxial mesoderm
Intermediate mesoderm
Lateral mesoderm

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2
Q

What is the mesoderm closest to the neural tube (either side)

A

Paraxial mesoderm

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3
Q

What is the mesdoerm which sits under the flat ectoderm

A

Lateral plate mesoderm

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4
Q

What is the mesoderm which sits between the paraxial mesoderm and the lateral mesoderm

A

Intermediate mesoderm

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5
Q

What is the mesoderm which also makes up the notochord

A

Axial mesoderm

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6
Q

Intermediate mesoderm gives rise to

A

Gonads and Kidney

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7
Q

Paraxial mesoderm gives rise to

A

Head and the somites

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8
Q

Somites give rise to

A

Skeletal muscle
Endothelila cells
Dermatome
Sclerotome

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9
Q

Sclerotome gives rise to

A

Cartilage and tendons

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10
Q

Lateral plate mesoderm gives rise to

A

Extraembryonic
Splanchnic
Somatic

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11
Q

Somatic meso gives rise to

A

Body cavity - pelivis - limbs and bones

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12
Q

Splanchnic meso gives rise to the

A

Circulatory system

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13
Q

What are somites

A

Segmented paraxial mesoderm tissues

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14
Q

Where do somites form

A

Pre-somitic mesoderm

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15
Q

What are earliest evidence for segmentation in vertebrates

A

Somites

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16
Q

How can meosderm segmentation be visualised

A

Engrailed 1 expression

Can see clear segmentation in the different organisms

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17
Q

Humans born with how many vertebrae

A

33

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18
Q

Humans adult how many vertebra and how many fused

A

24 vetebraes and 9 fused ones

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19
Q

How many somites in humans

A

38-44

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20
Q

How many somites in chick

A

55

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21
Q

How mnay somites in the mouse

A

65

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22
Q

How many somites in zebrafish

A

33

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23
Q

Paraxial mesoderm forms in a continuous manner until

A

Proper somite number is reached

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24
Q

The primitive streak is present until

A

Somites no longer form

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25
Q

Presomitic mesoderm prefigures

A

Future segmentation of the somites

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26
Q

Size of the presomitic mesoderm is equivilant to

A

12 somites

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27
Q

Formation of somites preceeds in a

A

A –> P

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28
Q

Why does the length of the paraxial mesoderm remain the same

A

Processes are cordinated

Formation of new somites and the extension of the paraxial mesoderm

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29
Q

What must cells within the presomitic mesoderm respond to

A 
Positional information 
Mechanism coordinating L and R somites 
Mechanism generating anterior boundary 
Mechanism generating posterior boundary 
Formation of the cleft
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30
Q

Describe the clock and wavefront model

A

Predicts a clock ticks in the posterior presomitic mesoderm - drives a molecular oscilatory that dictates the periodicity of somites
Where cells hit the travelling wavefront, an abrupt change of property occurs leading to the decision to form somites

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31
Q

Hairy gene
IN CHICK
IN MOUSE
IN ZEBRAFISH

A

c-Hairy-1
Hes
her

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32
Q

Describe the expression of c-hairy

A

At 0 mins high
Then falls
Then increases and peaks

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33
Q

Hairy/hes/her are targets of

A

Notch signalling

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34
Q

Hairy/hes/her proteins are

A

bHLH transcriptional repressors

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35
Q

Describe the feedback of Hes

A

Notch activates Hes1
Hes1 mRNA interacts with Hes1 protein
Caused poly ubiq of Hes1 protein and degredation
Hes1 protein represseses Hes1 ttranscription

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36
Q

This negative feedback on Hes1 means

A

Hes1 protein and Hes1 mRNA are expressed at different levels at different times

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37
Q

Effect of Hes1 mRNA

A

Poly ubiqu and degredation of of Hes1 protein

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38
Q

Effect of Hes1 protein

A

Repression of Hes1 transcriptin

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39
Q

Clock genes are targets of which signalling pathway

A

Notch
Wnt
FGF

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40
Q

Travelling wavefront tells cells that

A

They now need to form somites

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41
Q

After how many oscilations will a cell find itself in the anterior part of the presomitic mesoderm

A

12

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42
Q

Which was does the travelling wavefront move

A

Posteriorly

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43
Q

Determination front positioned where

A

At interface of RA gradient and FGF8 gradient

44
Q

what is posteiror

A

Pasraxial mesoerm

45
Q

Why is RA high anteriorly

A

Somites produce an enzyme required for the synthesis of RA

46
Q

What is used to ensure there is very little overlap of the FGF8 and RA gradient

A

Negative regulation

47
Q

Effect of RA of FGF8

A

RA inhibits FGF8

48
Q

What is the effect of cyp26

A

Cyp26 activated by FGF8

Cyp26 represses synthesis of RA

49
Q

What is the effect of Raldh2

A

Inhibited by FGF8 - activates Ra

50
Q

Where Hi FGF8 ___ Ra

A

Lo

51
Q

Where Hi RA ____ FGF8

A

Hi

52
Q

FGF8 expression induced ______ which acts with ______ to cause expression of Mesp2

A

TBX6

Notch

53
Q

Describe the initial expression of Mesp2

Describe where Mesp2 becomes localised to

What is the mechanism for this localisation

A

Whole of the prospective somite

Mesp2 becomes localised to the anterior

Mesp2 drives expression of ripply2 - which is a negative regulator of Mesp2

54
Q

What occurs if you transplant cells from a prospective somite boundary region into a non boundary regions

A

Leads to the formation of a boundary

55
Q

What do boundary cells do

A

Instruct cells that are anterior to form a boundary

56
Q

Lunatic frinfe AKA

what is the ffect of lunatic fringe

A

Glycosyltransferase

Inhibitor of notch

57
Q

Describe what happens when you force expression of lunatic fringe

A

Inducing lunatic fringe expression induces a new boundary

58
Q

what two things does notch drive

A

Boundary formation

Control Mesp2 production

59
Q

Describe the phenotype for a delat-like 3 mutant

A

Skeletal abnormalities since there isnt periodic segmentation of the somite

60
Q

Delta, notch and Mesp2 control

A

Expression of cell adhesion molecules

61
Q

What is an example of a cell adhesion moleucle controled by delta/notch and Mesp2

A

Ephron

62
Q

The changing in cell adhesion is coupled to

A

Epithelial to mesenchymal transition

63
Q

Describe the appearacne of the presomitic mesoderm - what does it contain

A

Unsegmented

Contains potential for 12 prospective somites to form

64
Q

What is the process which forms more paraxial mesoderm

A

Gastrulation

65
Q

Preiodicicity is dictated by

A

A clock which generates a molecular oscilator

66
Q

What is periodicity coupled to

A

The travelling wavefront

67
Q

Period of oscialtion is equivilant to

A

The time taken for a new somite pair to form

68
Q

What do cells in the position somite -1 decide to form

A

Somites

69
Q

Which axis is the first to be laid down during embryonic development

A

Anterior-posterior axis

70
Q

Which germ layer forms at the primitive streak during gastrulation

A

Mesoderm

71
Q

What experimental method lead to the identification of the origin of mesodermal tissue development

A

Lineage tracing

72
Q

What determines the adoption of different mesodermal fates in the developing embryo

A

Where the cells ingress along the anterior-posterior axis into the primitive streak

73
Q

Put these different mesodermal tissue types in order from most anterior to most posterior. Intermediate mesoderm, axial mesoderm, lateral mesoderm, paraxial mesoderm

A

Axial mesoderm, paraxial mesoderm, intermediate mesoderm, lateral mesoderm

74
Q

The axial mesoderm is one of the mesodermal tissues formed by the ingression of cell into the primitive streak, what two subtypes of mesoderm does it give rise to and where

A

Prechordal mesoderm (anteriorly) and the notochord (posteriorly)

75
Q

Which mesodermal tissue gives rise to the somites

A

Paraxial mesoderm

76
Q

Cells that ingress posteriorly to the paraxial mesoderm give rise to which tissue

A

Intermediate mesoderm

77
Q

The more posterior a cell ingresses into the primitive streak, the more posterior the mesoderm it will give rise to will be, T or F

A

F – more posterior ingress, the more lateral the mesoderm

78
Q

Alike the axial mesoderm, the posterior paraxial mesoderm is also subdivided, what are these subdivisions

A

Unsegmented posterior paraxial mesoderm and the segmented posterior paraxial mesoderm that give rise to somites

79
Q

What structures do the intermediate mesoderm give rise to

A

Kidneys and gonads

80
Q

How many components is the lateral mesoderm divided into and what do these divisions give rise to

A

The lateral mesoderm divides into 3 components, two of which give rise to the circulatory system and the other which contributes to extraembryonic structures and limb bones

81
Q

List the structures that the paraxial mesoderm give rise to

A

Axial skeleton, heart, somites, cartilage and tendons

82
Q

The formation of somites occurs in a sequential manner on both sides with the size of somites being preserved throughout, T or F

A

T

83
Q

The pre-somitic mesoderm is unsegmented, T or F

A

T

84
Q

Describe the rough structure of the somites viewed as a horizontal cross section

A

The somites show a clear metameric structure with a clear repeating pattern and defined anterior and posterior boundaries

85
Q

Somites are the earliest evidence of segmentation in vertebrates, T or F

A

T

86
Q

How do the number of somites relate to segmentation in vertebrates such as humans

A

Somite number dictates the number of vertebrae

87
Q

How many somites are present in humans and how does this relate to their segmentation

A

The human embryo has between 38 and 44 somites, this correlates to the 33 vertebrae which we are born with

88
Q

The number of somites is fixed for any given species and the timing of somite formation remains constant, T or F

A

F – whilst the number of somites does differ between species, so too does the timing of somite generation

89
Q

What five factors must cells in the paraxial mesoderm be able to respond to

A

Positional information, mechanisms that coordinate left and right, anterior and posterior boundary formation and the formation of the cleft

90
Q

What structure separates the left and right somites

A

Spinal cord

91
Q

What model describes the periodicity of somite formation and how is this achieved

A

Clock and wavefront model. The clock explains the temporal component whilst the wavefront provides spatial information to drive somite formation. Where cells hit the travelling wavefront an abrupt change of property leads to the decision to form somites

92
Q

Explain how a molecular oscillator drives mesodermal segmentation in chick embryos

A

In the embryo levels of the helix-loop-helix transcription factor C-hairy was found to fluctuate at different embryonic stages. Later genes were discovered that regulate the timing of this clock oscillation and are members of the notch, wnt or FGF signalling pathways

93
Q

What is meant by the determination front

A

Wavefront that travels from the anterior part of the presomitic mesoderm towards the posterior embryo

94
Q

How does the determination front dictate somitigenesis

A

When the cells of the paraxial mesoderm encounter oscillations from the molecular clock an abrupt change determines their formation of the next somite pair

95
Q

What aspect of the paraxial mesoderm determines somite boundary formation

A

Position of the somite minus II (S-II)

96
Q

Explain the results of ectopic grafting of boundary cells

A

Somite boundary cells isolated from one embryo transplanted into another embryo is sufficient to induce the formation of a new boundary. Where you’d expect to see one somite you would now get two. This shows that boundary cells instruct cells that are anterior to it to form a boundary

97
Q

What family of genes were discovered to be expressed at the somite boundaries

A

Notch family genes. They are selectively expressed in the anterior or posterior part of the somite

98
Q

Explain the results of forced lunatic fringe expression in the paraxial mesoderm and the significance of this

A

Lunatic fringe is a gene that blocks notch activity and thus forced expression results in an inhibition of notch signalling. This results in the formation of a new boundary and hence an additional somite

99
Q

Give an example of a human disease that proves a role of notch signalling in mesodermal segmentation

A

Jarcho Lewin syndrome causes spondylocostal dysplasia due to problems with the segmentation of the axial skeleton. This occurs due to a mutation in the delta 3 ligand that alters notch signalling and problems with somite segmentation

100
Q

Explain how the determination front is positioned

A

The determination front is determined at the interface of two opposing gradients. Retinoid acid which is high anteriorly and fibroblast growth factor 8 which is high posteriorly. When these gradients are equal the determination front forms.

101
Q

Where is retinoic acid produced to dictate determination front positioning

A

Somites

102
Q

RA and FGF8 agonise eachother, T or F

A

F – they antagonise each other

103
Q

Explain how RA and FGF8 interact to dictate determination front positioning

A

High levels of FGF8 result in high levels of Cyp26 which inhibits RA synthesis. High levels of FGF8 also inhibit the production of the Rhald2 enzyme that is normally required for RA synthesis

104
Q

What transcription factor do RA and FGF8 regulate the expression of

A

Mesp2

105
Q

How do RA and FGF8 interact to regulate expression of transcription factor(s) involved in somite boundary formation

A

RA activates Mesp2 expression whilst FGF8 inhibits it. Mesp2 expression in turn blocks local Notch signalling. Lower Notch signalling on one side of the border results in high notch signalling in adjacent cells on the other side of the boundary.

106
Q

What are the downstream effects of opposing notch signalling in cells either side of the boundary

A

High notch acitivity in one side and low activity in the cells opposite leads to formation of the somite boundary. The boundary itself forms from physical formation of cleft within the mesenchymal tissue. Downstream extensive changes in cell morphology and adhesion leads to creation of this cleft and is mediated by ephs and ephrins

BMS242 Developmental Biology (17 decks)

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