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BMS 242 - Principles of Developmental Biology > Mesoderm segmentation > Flashcards

Mesoderm segmentation Flashcards

1
Q

Where does gastrulation in the chick embryo occur?

A

At the primitive streak

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2
Q

What forms at the primitive streak during gastrulation?

How?

What else do these cells give rise to?

A

Mesoderm

  • Inward migration of the epiblast
  • Cells undergo ETM transition at the primitive streak
  • Cells emerge underneath the epithelial layer and contribute to the mesoderm

Give rise to a SMALL part of the endoderm

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3
Q

Do all the cells emerging at the primitive streak contribute to the same cells of tissues in the mesoderm?

A

No

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4
Q

What do lineage fate mapping studies in the chick show?

What does this show?

A

Point of entry within the primitive streak DICTATES the sorts of tissues that the cells contribute to

Shows that along the AP axis of the early epiblast - already designated regions that are fated to contribute to different areas of mesoderm

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5
Q

What do the cells at the VERY ANTERIOR of the PS become?

Early in the PS?

Slightly more posterior?

Even more posterior?

A

Axial mesoderm

Paraxial mesoderm

Intermediate mesoderm

Lateral plate mesoderm

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6
Q

What does the axial mesoderm give rise to?

A

Prechordal mesoderm

Notocord

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7
Q

What does the paraxial mesoderm give rise to?

A

Head

Somites

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8
Q

What does the intermediate mesoderm give rise to?

A

Urogenital system:

  • Kidneys
  • Gonads
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9
Q

What does the lateral plate mesoderm give rise to?

A

Circulatory system
Pelvis
Limb bones

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10
Q

What do somites give rise to?

A 
Cartilage
Tendons
Skeletal muscle 
Dermis
Endothelial cells
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11
Q

What is the dermatome?

A

The dermis and the skeletal muscle

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12
Q

What is the sclerotome?

A

The cartilage

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13
Q

What is the syndotome?

A

The tendons

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14
Q

What is the mytome?

A

The skeletal muscles

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15
Q

What are somites?

A

SEGMENTED paraxial mesoderm tissues

The earliest evidence of segmentation in vertebrates

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16
Q

Describe the most posterior paraxial mesoderm

A

NOT segmented - uniform band of tissue made of MESENCHYMAL cells

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17
Q

What happens are certain points in time at the very posterior paraxial mesoderm?

A
  • Formation of WELL-DEFINED balls of EPITHELIAL cells
  • That are REGULAR and EQUAL size on either side of the spinal cord
  • Clear clefts in between each ball
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18
Q

Is mesoderm segmentation highly conserved?

A

Yes

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19
Q

What are the advantages of segmented organisation in some structures?

Example of this?

A
  • Can introduce slight changes in otherwise well conserved units
  • To confer NEW PROPERTIES to the body

Example:

  • Some fish species - number of somites vary
  • Confer new properties throughout evolution
  • Allowing fish to change their swimming pattern and adapt to environment
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20
Q

What does the somite number dictate?

A

The number of vertebrae

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21
Q

How do somite numbers differ between organisms?

A

Number of somites between different species differ

But are SPECIES SPECIFIC

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22
Q

How do somites form?

A

In pairs from the paraxial mesoderm, through PROGRESSIVE SEGMENTATION:

  • Cells are produced in the posterior of the embryo
  • Cells remain in the paraxial mesoderm for a CERTAIN PERIOD of time - eventually become segmented to form somites
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23
Q

What 2 things occur until there are no more somites to be formed?

A

1) Paraxial mesoderm forms in continuous manner in the posterior of the embryo
2) Primitive streak is present

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24
Q

During somite formation what remains constant?

A

The TIMING of somite formation in a given species

Amount of somites in each species

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25
Q

What prefigures the future segmentation of somites?

A

Presomatic mesoderm (band of non-segmented, posteriror paraxial mesoderm)

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26
Q

How are new paraxial mesoderm (presomatic mesoderm) cells produced in the posterior?

A

Movement of cells through the primitive streak (through ETM transition) and emerging as new paraxial mesoderm cells

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27
Q

How does the length of the paraxial mesoderm remain the same?

A

2 processes are coordinated:

1) Body axis extend posteriorly
2) Anterior cells decide to become somites

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28
Q

How long is the presomatic mesoderm in the chick?

A

Contains about 12 somite pairs

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29
Q

What 5 must the cells in the presomatic mesoderm respond to?

A

1) Positional information
2) Mechanism that coordinates left and right somites
3) Mechanism that generates ANTERIOR boundary
4) Mechanism that generates POSTERIOR boundary
5) Formation of the cleft

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30
Q

Why must the cells in the presomatic mesoderm know their position?

A

Dictates if they are preparing to become somites or not

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31
Q

Why must cells in the psm respond to mechanism that coordinates the left and right somites?

A
  • Somites on either side are separated by a PHYSICAL boundary (spinal cord)
  • Somites must communicate as process in opposite sides happen at the same time/manner (eg. somite formation)
32
Q

What is the ‘clock and wavefront’ model?

A

Model that explains the regulation the periodicity of somite formation

33
Q

What 2 essential components does the ‘clock and wavefront’ model have?

A

1) Predicts a ‘clock’ ticks in the posterior part of the psm and drives a MOLECULAR OSCILLATOR, which dictates the PERIODICITY of the somites
2) Where cells hit the travelling WAVEFRONT - abrupt change of property, leading to the decision to form somites

34
Q

Where do somites form?

A

Anterior to progressing Hensons node

35
Q

What does somite formation happen at the same time as?

A

Growth of the presomatic mesoderm

36
Q

Describe the ‘clock and wavefront’ model of somite formation

A
  • Oscillations in gene expression
  • Cycles of gene expression that travel from posterior to anterior
  • Duration of each cycle/oscillation - time taken for a new pair of somites to form
  • Wavefront passes anterior –> posterior
  • When the wavefront means the oscillations of the molecular oscillator - series of changes in gene transcription occur that tell the cells to become somites
37
Q

What is the ‘wavefront’?

In which direction does it travel?

A

The wave of somite determination

Travels from anterior –> posterior

38
Q

How long does it take for an oscillation to occur in the chick?

Why is this important?

A

90 minutes

This is important as this is how long it takes for a new somite pair to form

39
Q

What is Hairy?

A

A family of transcription factors (repressors)

In drosophila

40
Q

What is the homologue of hairy in mice (mammals)?

41
Q

What is the homologue of hairy in zebrafish?

42
Q

What is the function of the Hairy/Hes/Her proteins?

A

bHLH (basic helix-loop-helix) transcriptional REPRESSORS

43
Q

What is critical for the oscillatory pattern of Hairy/Hes/Her protein?

A

Half-life and function

44
Q

What controls the gene expression of Hairy/Hes/Her?

A

NOTCH signalling

45
Q

What genes do Hairy/Hes/Her proteins repress?

What happens when the proteins are made?

A

THEMSELVES through negative feedback

So, when the proteins are made - decrease in mRNA levels (due to repression)

46
Q

Why is there an oscillation in Hairy/Hes/Her mRNA levels?

A
  • mRNA made
  • After a short delay, protein is made
  • Protein is a transcriptional repressor - represses the expression of Hairy/Hes/Her genes in negative feedback
  • mRNA decrease
  • Protein = very unstable
  • Repression of mRNA is rapidly decreased
  • Transcription of mRNA can now occur
47
Q

As well as Hairy/Hes/Her genes, what other genes show oscillatory expression?

A

Target genes of the Wnt, Notch, FGF signalling pathways

48
Q

How many oscillations do presomatic mesoderm cels undergo before becoming somites?

How does this work?

A

12

  • Presomatic mesoderm contains 12 somite pairs
  • More mesoderm is made posteriorly (the cell doesn’t actually move)
  • After 12 oscillations - cell is at the anterior of the presomatic mesoderm
49
Q

What determines the position of the wave front?

A

The interface between 2 antagonising gradients in the posterior of the embryo:

1) RA - High anteriorly (where the somites are)
2) FGF8/Wnt - high posteriorly

50
Q

What is the precise position of the wave front?

A

Where the lower part of the 2 gradients (of RA and FGF8) meet

51
Q

Why is RA concentration high in the somites?

Why does the gradient for RA decrease as move posteriorly?

A

-Somites synthesise enzyme required for the synthesis of RA

Gradient decreases as move posteriorly - somites stop synthesising this enzyme

52
Q

What is another name for the travelling wave front?

A

The ‘determination front’

53
Q

What happens to the determination front as somites are formed?

Why?

A

It moves POSTERIORLY

Due to RA gradient moving posteriorly: somites are continuously formed

AND

FGF8 gradient moving posteriorly: Mesoderm is continuously being made

54
Q

What does the position of the wavefront determine?

A

The timing of somite formation decision

55
Q

What maintains the reverse relationship between RA and FGF8?

A

Negative feedback regulations:

  • RA blocks production of FGF8
  • FGF8 ACTIVATES expression of Cyp26 and BLOCKS the transcription of Raldh2
56
Q

What is Cyp26?

A

A NEGATIVE regulator of RA production

57
Q

What is Raldh2?

A

Enzyme required for the synthesis of RA

58
Q

What is S1?

A

Somite 1: the most recently formed somite

59
Q

What is S0?

A

Somite 0: in the process of somite formation

60
Q

What is S-1?

A

Somite -1: Block of cells that have been specified to become somites

61
Q

Where does the oscillatory gene expression meet with the travelling wavefront?

A

At somite-1

62
Q

What occurs at somite-1, when the oscillatory clock meets the travelling wavefront?

A

1) FGF fate drives the expression of Tbx6
2) Tbx6 and Notch signalling combine to drive the expression of Mesp2
3) Meps2 is then expressed throughout the whole of S-1
4) Mesp2 drives the expression of Ripply2
5) Ripply2 rapidly restricts the expression of Mesp2 to the ANTERIOR compartment of S-1
6) Mesp2 inhibits Notch signalling through inhibiting DII 1 (which activates Notch signalling)
7) Notch signalling is confined to the posterior of the somite

63
Q

What is Tbx6?

A

A transcription factor that is driven by the expression of FGF

64
Q

What is Ripply2?

What is the expression of Ripply2 driven by?

A

A negative regulator of Mesp2

Driven by the expression of Mesp2

65
Q

Describe the gene expression pattern in S0

A

Ripply2 expressed - blocking the complete transcription of Mesp2

66
Q

What can the boundary cells of somites induce?

What is the evidence to show this?

A

Somite boundary formation

Evidence:
- Transplant anterior boundary cells from quail into the centre of a somite in the chick

  • Formation of a boundary and cleft in the transplanted region
67
Q

What family of genes are expressed at the somite boundary?

How are they expressed?

A

Notch family of genes

Differential expression of Notch/Delta between the anterior and the posterior of the somite

68
Q

What does ‘lunatic fringe’ encode?

A

Encodes a protein that INHIBITS notch signalling

69
Q

What happens when lunatic fringe is inserted into the centre of the chick somite?

What does this show?

A

Creates a new boundary

Shows that inhibition of notch signalling is SUFFICIENT to drive boundary formation

70
Q

How is there a coordination between the determination front and the formation of somite boundaries?

A

Notch signalling (which drives boundary formation) and is implicated in the control of Mesp2 expression (which is upregulated at the travelling wave front

71
Q

In a delta-3 mutation, what is caused?

Why?

A

Skeletal defects that arise throughout embryonic development as a result of not being able to have PERIODIC SEGMENTATION of somites

Due to the absence of Notch signalling

72
Q

How do somites physically form?

A
  • Delta and Notch signalling controls the expression of ephrins (adhesion molecule)
  • Ephrins LOCALLY increase cell adhesion - MTE transition
73
Q

How do Delta and Notch signalling control the expression of ephrins?

A

Either DIRECTLY
OR
Through controlling the expression of Mesp2

74
Q

What is expressed in the anterior of the somite?

A

Notch1 and Delta1

75
Q

What is expressed in the posterior of the somite?

A

Notch2 and Delta3

76
Q

When do somites aquire anterior and posterior identity?

A

During segmentation

77
Q

What is the onset of the oscillator?

A

Activation of c-Hairy1 and Luntatic fringe

BMS 242 - Principles of Developmental Biology (16 decks)

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