Somitogenesis Flashcards

1
Q

What are somites?

A

• Somites are transient embryonic structures that form many structures

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2
Q

What do somites form?

A
  • Somites form most of the bones in the trunk of the skeleton and bones on the base of the skull are formed from somites. The appendicular skeleton is not formed from somites
  • Almost all of the muscles are derived from somites, both on the trunk and appendicular regions.
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3
Q

What do somites form from?

A

Pre-somatic mesoderm (PSM)

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4
Q

Describe the order in which somites form?

A

Cranial -> caudal

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5
Q

What do somites form in the body?

A
•	Axial skeleton – somites
o	Vertebrae, ribs (not sternum)
•	Axial muscles – somites
o	Vertebral, thoracic, abdominal
•	Appendicular muscles – somites
o	Flexors, extensors
•	Appendicular skeleton – limb buds – not formed from somites
•	Limbs, digits, girdles
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6
Q

What are the divisions of the paraxial mesoderm which component forms the somites?

A

• The paraxial mesoderm is divided along the anterior-posterior axis. At the cranial end we have the head mesoderm, at the trunk is the somatic mesoderm.

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7
Q

What will the sclerotome form?

What will the myotome form?

What will the dermatome form?

A

Bone

Muscle

Dermis

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8
Q

What generates the PSM which will form those somites?

A

• The presomitic mesoderm (PSM) is generated by the cranial (rostral) primitive streak & the tail bud, involving proliferation, specification and emigration

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9
Q

How many somites will form?

A

• The total number of somites formed is also characteristic of the species, independent of variations in embryonic size (e.g. zebrafish 33 pairs, human 44, mouse 65)

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10
Q

What does the PSM form before the somite is formed?

What do they differentiate into?

A

• Initially paired epithelial spheres each side of neural tube

• Differentiate to:
o Dermomyotome and sclerotome (vertebrae)
o Myotome: epimere, hypomere, limb muscle
o Dermatome: dorsal dermis
o Syndetome: tendons

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11
Q

Describe the organisation of the sclerotome and how it forms

A

Epithelial somites are present on each side of the neural tube at day 22

The epithelial somites will undergo epithelial to mesenchymal transition such as in gastrulation. The mesenchymal cells will migrate (they are sclerotomal) and will surround them neural tube and notochord.

The sclerotome cells will continue to proliferate and migrate. They will eventually surround the neural tube and the notochord.

The cells will go on to form the vertebrae that surround the neural tube (spinal cord)

They initially develop cartilage which is then mineralised by a process called endochondral ossification.

They will begin to form the transverse processes that will divide the epimer from the hypomere, so the dermatomyotome will form the epimer at the top and hypomere at the bottom

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12
Q

Describe the fate of the sclerotome

A

Sclerotome will form the centrum that surrounds the neural tube and notochord

The Notochord will form the intervertebral disks

Neural arches will surround the neural tube - fails you get spina abfinida

Sclerotome will also form the costal processes such as the ribs

Sternum forms from somatic mesoderm not somites

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13
Q

What does removal of the spinal ganglia and notochord cause?

A
  • If you remove the spinal ganglia, then the neural arches remain unsegmented so we know that the adjacent nerves are important in subdivision of the sclerotome
  • If you remove the notochord then the centrum remains unsegmented
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14
Q

What does the myotome cells form and how are they divided?

A
  • The myotome will form both the flexors and extensors of the trunk including the ventral wall muscles, distal ribs, dorsal and ventral muscles masses of limbs
  • We mentioned that the transverse processes will grow outwards from the sclerotome and will divide muscles into epimer (dorsal) and hypomere (ventral).
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15
Q

Where do myotome cells also migrate?

A

Into limb buds

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16
Q

Summarise what happens to the myotome cells

What else do the myotome cells form?

A

Myotome is divided into 2 parts: a dorsal and ventral portion called the epimere and hypomere

Epimere will form the extensors of vertebral column

Hypomere will form the flexors

  • Thorax - myoblasts form 3 intercostals (external, internal, innermost)
  • Abdomen - myoblasts form external, internal, transversus abdominis
17
Q

What is the epimere and hypomere innervated by?

A

Epimere - dorsal ramus of spinal nerve

Hypomere - ventral ramus of spinal nerve

18
Q

Describe the migration of the myoblast precursors into the limb

A

Limb buds emerge at the flank

Signals are released from the limbs that attract muscle cell precursors cells from the hypomere into the limb

Myoblasts vells divide into a dorsal and ventral muscle mass

Dorsal = extensors

Ventral = flexors

Myoblasts precursors are attracted to the limb bud by scatter factors (HGF) by mesoderm in limb bud. Hypomere attract express C-met (RTK receptor)

Nerves then grow form the neural tube into muscles

19
Q

What does the dermatomes form?

A

Dorsal dermis - migrates over the surface of the embryo

20
Q

What is the dermis innervated by?

A

• The stripes of dermis are then innervated by a single spinal ganglion. This is maintained along the anterior-cranial caudal axis

21
Q

On a separate note, how is differentiation of the somite controlled?

A
  • The ventral portions of the neural tube and the notochord will secrete Shh which acts upon the somite to cause the expression of a transcription factor called Pax 1 which marks sclertomal cells in the ventral and medial parts of the somites
  • There are signals that are released from the dorsal neural tube called Wnt. This causes the adjacent dermomyotome to differentiate towards an epimere fate and will express the transcription factor Myf5
  • The lateral plate of the mesoderm will secrete BMP4 along with Wnt signals from the dorsal part of the body wall. This will induce the expression of a transcription factor in the hypomere called MyoD.
  • NT-3 will induce the expression of Pax 3 which marks the dermatome compartment.
22
Q

Describe the segmentation of the sclerotome

A

Sclerotome has a cranial and caudal portion

Segmental arteries lie between the somites

Caudal part of the first somite will fuse with the cranial part of adjacent somite to form the centrum

Allows muscles to span over adjacent vertebrae to permit movement between vertebrae

Spinal nerves pass through the somites to run through intervertebral foramen

23
Q

Where does the syndetome lie?

What does it express?

Where is it found

A

Syndetome lies at the cranial end of the somite

Scx TF

At the block of each myotome territory

Permits the attachment of the muscles to the transverse process of each vertebrae

24
Q

What gives each somite a unique axial identity?

A

Expression of genes within PSM

Genes are expressed in the PSM that specify the axial position of the somite

25
Q

How are hox genes arranged and how do they work

A

• These hox genes are arranged along the chromosomes which are located adjacent to each other and expression along the AP axis correlates with the position along the chromosome.

  • Hox genes bind DNA in a sequence-specific fashion
  • They regulate expression of adjacent/nearby genes
  • Confer positional identity along the A-P (cranio-caudal) axis of the trunk
26
Q

How have hox genes arisen?

A

Arisen from duplication of an ancestral gene within the same organism

The chromosomal arrangement is conserved

Paralogues exists between specifies

3' = anterior
5' = posterior
27
Q

How many Hox gene clusters do vertebrates have?

How do these hox genes form a combinatorial pattern?

A

4

Arisen from 2 duplication events

Different expression of hox genes overlap specifying regional AP identity

28
Q

Relate Hox genes to somites

A

Hox genes give somites a different identity and morphological cell fate but cell types are the same.

Identity is encoded for by Hox genes in PSM

29
Q

What does the clock and wavefront model do?

A

Determines each somite boundary within the PSM

30
Q

Describe Tier 1 of the clock and wavefront model

A

Cyclical levels of protein and mRNA in cells within the PSM

Transcription and Translation delay is coupled with mRNA and protein instability

Hes/her TFs are cycled in a cell

  1. Hes/her gene transcription at a basal rate -> hes/her mRNA -> Hes/her proteins
  2. Hes/her proteins in cytoplasm
  3. Hes/her proteins translocate back into nucleus -> dimerise -> hes/her transcriptional repressors
  4. Repressors accumulate -> switch off hes/her transcription
  5. Gene products (mRNA, protein dimer) decay, transcription is switched on again
  6. Generates oscillation of mRNA and protein levels
31
Q

Describe Tier 2 of the clock and wavefront model

A
  1. Single cell oscillator is regulated by notch-delta signalling -> couples cells together so ossilication of mRNA and proteins are coordinated between cells
  2. Notch proceeds delta ligand and is transcribed and translated to cell membrane but only activated when delta is expressed on neighbouring cells
  3. Delta is transcribed in the nucleus -> post-translational modifications in the cytoplasm -> expressed on cell membrane
  4. DLL binds to notch -> notch intracellular domain (NICD) is transported to nucleus and Hes/her mRNA transcription -> peak of ossicilation
  5. Hes/her dimerization negatively feeds back on delta expression -> Less DLL at membrane -> less notch activation -> less hes/her transcription -> trough of oscillation
  6. Lunatic fridge modify notch signalling
  7. Cyclic genes belonging to Notch and FGF oscilate in the opposite pattern to wnt -> all three activate tbx6
32
Q

Describe Tier 3 of the clock and wavefront model

A

Morphogen gradient

Caudal: FGF and Wnt. FGF: mRNA decay and Wnt via protein decay

FGF enhances Wnt activity via Akt and GSK-3-beta

RA via RALDH2 cranially

33
Q

What happens at the determination front?

A
  1. Cells at the correct phase of cycling are competent to respond to the wavefront switching on Mesp2 expression and stop cycling

2, Notch in the presence of tbx6 induces the expression of Mesp2

  1. Mesp2 inhibits tbx6 and notch to the anterior domain of the forming somite
  2. In this anterior domain Notch is setting caudal identity of the next somite and Mesp2 marks the anterior boundary where the following somite will form
  3. EphA4 is also a downstream target of Mesp2 which will result in the production of ephrin B2 in adjacent border cells that drives the formation of the physical boundary between the adjacent somites.
34
Q

Where breaks left-right asymmetry of somite formation?

A

RA prevents LR asymmetry in PSM