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Developmental Biology > L11 - Mesoderm Segmentation > Flashcards

L11 - Mesoderm Segmentation Flashcards

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1
Q

Where does gastrulation take place?

A

Within the primitive streak

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2
Q

Where does the mesoderm form?

A

Within the primitive streak

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3
Q

What do cells arising from the primitive streak contribute to?

A

Not all cells arising from primitive streak contribute to the same tissues within the mesoderm

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4
Q

What experiments did hey use to determine what cells of the primitive streak became?

A

Using lineage fate map studies or directly labelling cells it was discovered that the point of entry of cells within the primitive streak dictates the tissues the cell will

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5
Q

What does axial mesoderm form?

A

Forms notochord and pre-chordal mesoderm

Comes from cells from Hendersons node

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6
Q

What does paraxial mesoderm form?

A

Forms head and somites – anterior

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7
Q

What does intermediate mesoderm form?

A

Forms kidneys and gonads

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8
Q

What does lateral mesoderm form?

A

Forms circulatory system, somatic tissue and extra embryonic tissue

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9
Q

What do somites form from?

A

Somites are segmented paraxial mesoderm tissue

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10
Q

Somites are evidence of?

A

Somites are the earliest evidence of segmentation in vertebrates

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11
Q

What part of the paraxial mesoderm is segmented?

A

Most posterior paraxial mesoderm is not segmented
Uniform band of tissues made of mesenchymal cells
Segmentation occurs as you move more anterior

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12
Q

What does somite number dictate?

A

The number of vertebrae

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13
Q

How many vertebrae do humans have?

A

Humans are born with 33 vertebrae

By adulthood - 24 vertebrae and 9 fused ones

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14
Q

How many somites do human embryos have?

A

38-44

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15
Q

How many somites do chick embryos have?

A

55

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16
Q

How many somites do mouse embryos have?

A

65

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17
Q

How many somites do zebrafish embryos have?

A

33

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18
Q

How do somites form?

A

Form in pairs from the paraxial mesoderm
They bud off the pre-somitic mesoderm
- Form every 90 min

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19
Q

What is the role of paraxial mesoderm in somite formation?

A

Paraxial mesoderm forms in a continuous manner until proper somite number is reached
Number of somites is fixed for a given species
Timing of somite formation remains constant within species

20
Q

What is the role of pre-somatic mesoderm in somite formation?

A

Pre-somitic mesoderm, although not segmented, pre-figures the future segmentation of somites
- Potential for 12 somite pairs

21
Q

How do you explain the periodicity and reproducibility of somite formation?

A

Cells within pre-somitic mesoderm must respond to

  • Positional information
  • Mechanism that coordinates left and right somites
  • Mechanism that generates anterior boundary
  • Mechanism that generates posterior boundary
  • Formation of cleft
22
Q

How is the periodicity of somite formation established?

A

Clock and wavefront model

Cooke and Zeeman - 1976

23
Q

What does the clock and wavefront model predict?

A

Predicts that a clock ticks in the posterior pre-somitic mesoderm and drives a molecular oscillator 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

24
Q

How was the oscillation of C-hairy expression in the pre-somitic mesoderm shows?

A

A series of in situ hybridisations

25
Q

What were the expression patterns of the gene when looking at the oscillation of C-hairy expression?

A

Expression patterns of the gene tended to fall into 3 classes

  • Large band of expression
  • Shorter band of expression
  • Shortest band of expression
26
Q

What pattern of gene expression did C-hairy follow?

A

Patterns expressed over a period of 90 minutes
Gene expression followed an oscillation pattern
After 90 min, a new somite pair had formed

27
Q

What is hair/hes/her protein useful for?

A

Their half life and function is critical for the oscillatory pattern of its mRNA

28
Q

What are hair/hes/her genes targets for?

A

They are target genes of notch signalling

  • When you have notch signalling
    • Genes are transcribed forming Hes1 proteins
    • Proteins repressors its own transcription
    • However, protein is unstable so quickly degraded
29
Q

Hair/hes/her proteins are?

A

bHLH transcriptional repressors

30
Q

The proteins synthesised by hair/hes/her have?

A

A very short half life

31
Q

The oscillatory patterns of hair/hes/her occurs via?

A

A negative feedback loop and an unstable proteins

32
Q

What are other examples of clock genes?

A

All belong to the Wnt, Notch and FGF signalling pathways

They display the same characteristics and expression patterns

33
Q

How many cycles of oscillations are there?

A

Pre-somitic mesoderm cells undergo 12 cycles of oscillations before forming somites

34
Q

What happens when cells encounter the travelling wavefront?

A

When cells encounter wavefront travelling in opposite direction oscillations stop

35
Q

The determination front is positioned where?

A

Determination front is positioned where the two opposing gradients meet

  • Retinoic acid
    • High anteriorly
    • Gradient high where somites are found
  • FGF8
    • High posteriorly
36
Q

What does the determination front determine?

A

Determines the timing of somite formation?

37
Q

What direction does the wavefront move?

A

Posteriorly

38
Q

How is the relationship between retinoic acid and FGF8 maintained?

A

Negative feedback regulations
Retinoic acid
- Blocks transcription of FGF8
FGF8
- Controls expression of Cyp26 which blocks transcription of retinoic acid
- Blocks the transcription of Raldh2 which promotes transcription of retinoic acid

39
Q

What does FGF8 promote transcription of?

A

Tbx6 which along with notch signalling promotes transcription of Mesp2

40
Q

What expression is maintained in somite -1?

A

Initially Mesp2 is expressed throughout
Mesp2 transcription generates protein which drives expression of Ripply2
Ripply2 is a negative regulator of Mesp2
Expression of Mesp2 restricted to anterior part of somite -1

41
Q

What expression is maintained in somite 0

A

Ripply2 also represses Mesp2

Very narrow band of expression of Mesp2

42
Q

How can boundary cells induce somite boundary formations?

A

Transplantation of a prospective somite boundary region into a non-boundary region creates a new boundary
Shows that boundary cells instruct cells that are anterior to form a boundary

43
Q

Where are notch family genes expressed?

A

Expressed at the somite boundary

Notch signalling involved in somite boundary formation

44
Q

What gene construct was created to show the role of notch signalling in somite boundary formation?

A

Generated a gene construct - lunatic fringe
Codes for a protein which inhibits notch signalling
Introduced construct into chick embryo
- Forced the expression of this gene into central aspect of somite
- Created a new boundary
- Notch signalling is sufficient for boundary formation

45
Q

How are somite derivatives affected in the absence of Notch signalling?

A

Delta-like 3 mutant - ossification centres do not align

In humans a similar mutation causes spondylocostal dysplasia

46
Q

Summary of segmentation

A

Oscillation slows down as cells mature
Acquisition of anterior and posterior identity
Notch1 and Dl1 in posterior
Notch2 and Dl3 in anterior

47
Q

An example of a model of somite formation?

A
  1. Molecular oscillator
  2. C-hairy
  3. Lunatic fringe
  4. Delta 1 or Notch 1
  5. If notch1 - ephrins
  6. Cell adhesion changes
  7. Somite formation

Developmental Biology (16 decks)

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