Mesoderm A-P Patterning- Somites Flashcards

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1
Q

Explain mesoderm formation in the chick

A
  • First evidence of A-P axis forming is a ‘groove’ called the primitive streak which elongates anteriorly
  • Primitive streak is where gastrulation takes place
  • The cells migrate from the future ‘ectoderm’ to the centre where the PS is and fold inwards to the groove
  • The cells that migrate laterally rather than deeply will form the mesoderm
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2
Q

What is the primitive streak?

A
  • linear thickening on the surface of the epiblast (outer layer of the blastula)
  • crucial for gastrulation where cells migrate inward to form the 3 germ layers
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3
Q

What tissues are the mesoderm subdivided into?

A
  1. Axial mesoderm
  2. Paraxial mesoderm
  3. Intermediate mesoderm
  4. Lateral mesoderm
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4
Q

How did the subdivided mesoderm come about?

A
  • The paraxial mesoderm is subsequent to the axial mesoderm and forms from the cells that go into the primitive streak next to the Hensons node (relatively anterior)
  • Intermediate mesoderm is a thin line which runs A-P
  • Cells that enter the primitive streak most posteriorly form the lateral mesoderm
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5
Q

What does the axial mesoderm give rise to?

A

Anteriorly - Pre-caudal mesoderm
Posteriorly - notochord

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6
Q

Where do somites originate from and what is their role?

A
  • Originate from the segmented posterior end of the paraxial mesoderm
  • Contribute to formation of tendons, epidermis, endothelial cells and skeletal muscle
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7
Q

What do the intermediate mesoderm and the lateral plate mesoderm contribute to the formation of?

A

intermediate mesoderm = kidneys and gonads

lateral plate mesoderm = circulatory systems, pelvis and limbs

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8
Q

How is the paraxial mesoderm segmented?

A
  • Paraxial mesoderm is initially born in posterior part of the mesoderm and is initially non segmented
  • At some point we start seeing evidence of segmentation which proceeds posterior to anterior
  • Highly conserved evolutionary process
  • Forms ‘balls’ alongside the neural tube
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9
Q

How do somite’s contribute to the formation of vertebrae?

A
  • Diff. vertebrates have diff. number of somites and diff. number of vertebrae
  • THE REPEATED NUMBER OF SOMITES IS SPECIES DEPENDENT
  • The somite’s form during embryonic development but the timing of formation is also species dependent
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10
Q

How do somite’s form and what is occurring at the same time as somite formation?

A
  • Form in a sequential, continuous manner until species specific number is reached
  • At the same time of formation, gastrulation is happening in the posterior part of the embryo
  • New cells form in the paraxial mesoderm as the primitive streak elongates posteriorly
  • As the primitive streak elongates, somites are sequentially forming at the anterior part towards the new cells
  • Primitive streak is to be present until somites no longer form
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11
Q

What is the unsegmented pre-somitic mesoderm’s role in somtie formation?

A

Pre-figures the future segmentation of somites

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12
Q

What needs to be achieved in the non-segmented mesoderm for somite formation to occur?

A

Positional info and intrinsic awareness
- is the somite on the left or right for e.g.

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13
Q

How is the periodicity of somite formation established?

A

The ‘clock’ theory
- - something located in the P part of embryo which sets timing so cells that enter paraxial mesoderm understand how long they have to stay unsegmented in the axial mesoderm and when to form a somite
- Where cells meet the travelling ‘wavefront’ an abrupt change of property occurs to intiate somite formation

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14
Q

Explain c-Hairy oscillation signalling

A
  • Part of molecular clock theory via gene expression
  • c-Hairy is activated + transcribed in on phase of oscillation via Wnt and FGF8 signalling and subsequent Notch signalling
  • Negative regulation as the mRNA is not stable and the protein represses its own transcription
  • Results in the ‘off’ period of oscillation
  • Because the protein isnt very stable itself it cant halt transcription for long so the whole process begins again
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15
Q

How many cycles of oscillations do presomitic cells undergo before forming somites?

A

12

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16
Q

What is the wavefront of the ‘clock theory’

A
  • ‘Determination front’
  • defined by the front of the interface of two opposing gradients - Retinoic acid (coming from anterior) and FGF8 (coming from posterior)
  • position of which cells will stop oscillation and will establish stable expression patterns necessary for somite formation
17
Q

What genes are expressed at the determination front?

A
  • boundary-forming genes, including Ephrin-B2 and its receptor Ephrin A4
  • Important for defining the borders between adjacent somites
  • Found in the central part of future somite
  • Notch signalling is involved in this boundary cells, shown in KO mice where no notch leads to disruption of axial skeleton
18
Q

What is the interaction between Ephrin ligands and Ephrin receptors at somite boundaries?

A
  • Ephrin ligands (Ephrin-B2 and Ephrin A4) bind to their corresponding receptors to promote cell adhesion in the case of somite boundaries
  • The cells expressing these ligands are considered ‘boundary cells’.
  • The expression of these ligands is brought about by Mesp2 when the determination front is reached
19
Q

How is it ensured that there will be an interface between Retinoic acid and FGF8?

A
  • Retinoic acid prevents diffusion of FGF8 in the diffusion of where it is by blocking Erk
  • FGF8 stimulates transcription of Cyp26 which is a protein that degrades retinoic acid
  • Also prevents transcription of Raldh2 which is an enzyme needed for the synthesis of retinoic acid

ENSURES THEY ARE MUTUALLY EXCLUSIVE

20
Q

How do somites become polarised and why is this important?

A
  • Mesp2 is only expressed in the anterior portion of the future somite
  • Mesp2 transcribed via Tbx6 and Notch signalling
  • Mesp2 blocks the Delta1 required for notch signalling and will induce Ripply2 expression posteriorally which blocks Tbx6 (and therefore Mesp2) to ensure its only in the anterior portion