Somitogenesis Flashcards
What are somites?
• Somites are transient embryonic structures that form many structures
What do somites form?
- 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.
What do somites form from?
Pre-somatic mesoderm (PSM)
Describe the order in which somites form?
Cranial -> caudal
What do somites form in the body?
• 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
What are the divisions of the paraxial mesoderm which component forms the somites?
• 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.
What will the sclerotome form?
What will the myotome form?
What will the dermatome form?
Bone
Muscle
Dermis
What generates the PSM which will form those somites?
• The presomitic mesoderm (PSM) is generated by the cranial (rostral) primitive streak & the tail bud, involving proliferation, specification and emigration
How many somites will form?
• 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)
What does the PSM form before the somite is formed?
What do they differentiate into?
• 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
Describe the organisation of the sclerotome and how it forms
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
Describe the fate of the sclerotome
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
What does removal of the spinal ganglia and notochord cause?
- 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
What does the myotome cells form and how are they divided?
- 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).
Where do myotome cells also migrate?
Into limb buds
Summarise what happens to the myotome cells
What else do the myotome cells form?
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
What is the epimere and hypomere innervated by?
Epimere - dorsal ramus of spinal nerve
Hypomere - ventral ramus of spinal nerve
Describe the migration of the myoblast precursors into the limb
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
What does the dermatomes form?
Dorsal dermis - migrates over the surface of the embryo
What is the dermis innervated by?
• The stripes of dermis are then innervated by a single spinal ganglion. This is maintained along the anterior-cranial caudal axis
On a separate note, how is differentiation of the somite controlled?
- 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.
Describe the segmentation of the sclerotome
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
Where does the syndetome lie?
What does it express?
Where is it found
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
What gives each somite a unique axial identity?
Expression of genes within PSM
Genes are expressed in the PSM that specify the axial position of the somite
How are hox genes arranged and how do they work
• 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
How have hox genes arisen?
Arisen from duplication of an ancestral gene within the same organism
The chromosomal arrangement is conserved
Paralogues exists between specifies
3' = anterior 5' = posterior
How many Hox gene clusters do vertebrates have?
How do these hox genes form a combinatorial pattern?
4
Arisen from 2 duplication events
Different expression of hox genes overlap specifying regional AP identity
Relate Hox genes to somites
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
What does the clock and wavefront model do?
Determines each somite boundary within the PSM
Describe Tier 1 of the clock and wavefront model
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
- Hes/her gene transcription at a basal rate -> hes/her mRNA -> Hes/her proteins
- Hes/her proteins in cytoplasm
- Hes/her proteins translocate back into nucleus -> dimerise -> hes/her transcriptional repressors
- Repressors accumulate -> switch off hes/her transcription
- Gene products (mRNA, protein dimer) decay, transcription is switched on again
- Generates oscillation of mRNA and protein levels
Describe Tier 2 of the clock and wavefront model
- Single cell oscillator is regulated by notch-delta signalling -> couples cells together so ossilication of mRNA and proteins are coordinated between cells
- Notch proceeds delta ligand and is transcribed and translated to cell membrane but only activated when delta is expressed on neighbouring cells
- Delta is transcribed in the nucleus -> post-translational modifications in the cytoplasm -> expressed on cell membrane
- DLL binds to notch -> notch intracellular domain (NICD) is transported to nucleus and Hes/her mRNA transcription -> peak of ossicilation
- Hes/her dimerization negatively feeds back on delta expression -> Less DLL at membrane -> less notch activation -> less hes/her transcription -> trough of oscillation
- Lunatic fridge modify notch signalling
- Cyclic genes belonging to Notch and FGF oscilate in the opposite pattern to wnt -> all three activate tbx6
Describe Tier 3 of the clock and wavefront model
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
What happens at the determination front?
- 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
- Mesp2 inhibits tbx6 and notch to the anterior domain of the forming somite
- 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
- 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.
Where breaks left-right asymmetry of somite formation?
RA prevents LR asymmetry in PSM
