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Developmental biology extras > Lecture 11 Mesoderm AP patterning > Flashcards

Lecture 11 Mesoderm AP patterning Flashcards

1
Q

The organiser undergoes… to become…

A

convergent extension

rod of mesoderm in the middle called axial mesoderm, and bands of mesoderm either side called paraxial mesoderm

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2
Q

Which species was used to learn about the formation of paraxial mesoderm

A

Chick embryo

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3
Q

Difference between chick and xenopus embryo paraxial mesoderm

A

Flattened discs vs a fold with animal and vegetal poles

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4
Q

Describe the chick embryo as it is undergoing gastrulation

A

2 sheets of cells
Epiblast layer top
Hypoblast layer bottom

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5
Q

What is equivalent to the Xenopus organiser

A

Hensen’s node

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6
Q

Where does mesoderm form during gastrulation

A

At the primitive streak

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7
Q

At the 2 layer (epiblast/hypoblast stage), what occurs?

A

Signals from hypoblast change the fate of the epiblast

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8
Q

Which cells become endoderm

A

Cells that see a high conc of nodal

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9
Q

Which cells become mesoderm

A

Cells that see a lower conc of nodal

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10
Q

What are the four mesodermal tissues

A

Axial mesoderm
Paraxial mesoderm
Intermediate mesoderm
Lateral mesoderm

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11
Q

Mesoderm that forms immediately adjacent to the axial mesoderm/either side of the NT is..

A

Paraxial mesoderm

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12
Q

What is the mesdoerm which sits under the flat ectoderm i.e. the furthest away

A

Lateral mesoderm

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13
Q

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

A

Intermediate mesoderm

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14
Q

What is the mesoderm which also makes up the notochord

A

Axial mesoderm

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15
Q

Intermediate mesoderm gives rise to

A

Gonads and kidney

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16
Q

Paraxial mesoderm gives rise to

A

Head anteriorly

Somites at the trunk

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17
Q

Somites give rise to

A
  • Sclerotome/cartilage
  • Syndotome/tendons
  • Myotome/skeletal muscle
  • Dermatome/dermis, skeletal muscle
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18
Q

Lateral plate mesoderm gives rise to

A

Extraembryonic
Splanchnic
Somatic

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19
Q

What are somites

A

Segmented paraxial mesoderm tissues

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20
Q

What is pre-somatic mesoderm

A

Where the somites form, at the posterior

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21
Q

What are somites the earliest evidence of

A

Segmentation in vertebrates

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22
Q

How can meosderm segmentation be visualised

A

Engrailed 1 expression
Can see clear segmentation in the vertebrates and invertebrates as mesodermal segmentation is conserved throughout evolution

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23
Q

What does somite number dictate

A

Number of vertebrae

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24
Q

Somites form in… from the paraxial mesoderm

A

Pairs

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25
Paraxial mesoderm forms in a ….. until ….
Paraxial mesoderm forms in a continuous manner until the proper somite number is reached
26
What is true about somites for a given species
Number of somites is fixed | Timing of somite formation is constant
27
Why can we determine age of embryo
Number of somites as time constant for somite formation
28
Is presomitic mesoderm segmented
No
29
In which direction do somites form
A --> P
30
Describe series of events leading to epithelialisation of somites
1. Gastrulation: acquisition of paraxial mesoderm identity 2. Onset of oscillator: activation of c-Hairy1 and Lunatic Fringe 3. Segmentation: Oscillation slows down as cells mature. Acquistion of A and P identity Notch1/ Dl1 in post Notch2/Dl3 in ant 4. Determination front: Forms at interface of 2 opposing gradients 5. Somitogenesis: epithelialisation of somites
31
Is the PSM composed of uniform cells?
No It is composed of cells that are gradually expressing an oscillating time i.e. the clock which is constantly turned on and off
32
What will the clock hit? After how many cycles?
Determination front | 12 cycles to form 12 somites
33
Where does this determination front form?
Interface of the 2 opposing gradients
34
What does the determination front result in?
PSM will undergo somitogenesis to form somites via epithelialisation
35
How often do somites form in chicks?
Every 90 minutes
36
How is the periodicity of somite formation established?
The clock and wavefront model (Cooke and Zeeman, 1976)
37
What does the clock and wavefront model predict
• Predicts a ‘clock’ ticks in the posterior PSM and drives a molecular oscillator that dictates that periodicity of somites
38
What happens to cells in PSM when they hit the travelling wavefront
• Where cells hit the travelling wavefront (determination front), an abrupt change of property occurs leading to the decision to form somites
39
Which 2 independent phenomena account for periodic somite formation?
1. an intrinsic biochemical oscillator, clock, by which cells oscillate synchronously between a permissive and a non-permissive state of somite formation 2. maturation front travelling along the embryonic AP axis, moving posteriorly in concert with the AP differentiation gradient of the embryo, the wavefront
40
What state must be the cells in the PSM be in for a somite to form
• For a somite to be formed, a group of PSM cells in the permissive state of the clock must be reached by the wavefront of differentiation
41
Cells within PSM must respond to what x4?
* Positional information * Mechanism that coordinates left and right somites * Mechanism that generates posterior boundary * Formation of cleft between each somite
42
What was the first evidence of a clock model?
In situ hybridisation for Notch signalling pathway components
43
Hairy gene IN CHICK IN MOUSE IN ZEBRAFISH
c-Hairy-1 Hes her
44
Describe the expression of c-hairy
At 0 mins high Then falls Then increases and peaks
45
Hairy/hes/her are targets of
Notch signalling
46
What are Hairy/hes/her described as
bHLH transcriptional repressors
47
Clock genes are targets of which signalling pathway
Wnt FGF Notch
48
After how many oscilations will a cell find itself in the anterior part of the presomitic mesoderm
12
49
How long will it take to form a somite
12x90 min | Approx 18 hours
50
Where are somites specified
Determination front
51
S0 marks
where the cell has just past the determination front
52
S-1 marks
the specification of boundary formation (this cell has gone through 12 oscillations)
53
When do oscillations stop
• When cells encounter the wavefront travelling in opposite direction, oscillations stop
54
Where is the determination front positioned?
At the interface of 2 opposing gradients i.e. at interface of RA gradient and FGF8 gradient
55
Describe the gradients of FGF8 and retinoic acid
- FGF8 gradient is highest at the posterior end of the paraxial mesoderm. FGF8 is expressed at lowest levels anteriorly - Retinoic acid is expressed in early forming somites, but they have to have already formed, highly expressed anteriorly
56
What maintains the reverse relationship between RA and FGF8 gradients?
Negative feedback regulations maintain the reverse relationship between RA and FGF8 gradients
57
Draw out the negative feedback regulations to maintain reverse relationship
See notes
58
What is expressed at a somite boundary?
Notch family genes
59
Describe notch expression at the boundary of somites
* Delta 1/Notch 1 only expressed in P part of the first forming somite * Delta 3/Notch 2 only expressed in A part of the first forming somite
60
When are these genes upregulated
Only after the determination front when oscillations stop
61
How are the Notch family of genes set up due to the molecular clock
• In some way, the molecular clock as it ticks through permissive/non-permissive sets up bands of these different genes
62
How would the Notch family of genes be described in somite boundary formation
Instructive
63
How do we know that Notch signalling is important in somite boundary formation?
Gain of function | Loss of function
64
Describe gain of function experiment in Notch singallign somite boundary formation
* You electroporate in a component of the notch signalling pathway e.g. lunatic fringe, into an ectopic position * Lunatic fringe is not normally expressed inbetween 2 somites * Consequences are that you get an extra small somite forming as Lunatic fringe give a 2nd A and P boundary
65
What is lunatic fringe
• Lunatic fringe is a glycosyltransferase which is an inhibitor of notch
66
Describe loss of function experiment in Notch signalling somite boundary formation
* Predict fewer somites or somite derived structures * In a mouse mutant which lacks Delta-like 3 (normally for formation of A part of somite), then you can see that you have fewer ribs, not proper formation and budding of somites in the anterior portion
67
In human, a mutation in delta 3 causes what
• In humans, a similar mutation causes spondylocostal dysplasia (Jarcho Lewin Syndrome) – 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
68
How do ephrins play a role in control of somite formation?
* Ephrins usually associated with keeping 2 cells separate (mutual repellents) * Ephrins cause cell adhesion changes which cause the budding and integrity of the single somite

Developmental biology extras (13 decks)

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