Somitogenesis Flashcards
What is the wavefront?
The constant gradient of FGF8 to the posterior end. Need this in order to form somites (high concentration at the posterior end of the presomatic mesoderm). Need RA to inhibit FGF8 to a certain threshold when somites begin to form.
What is the clock?
The cyclic activation of Wnt signalling as well as downstream genes. (This sets location and timing for somite separation)
What do somites form from?
The paraxial mesoderm
Where is BMP activity the lowest in the mesoderm?
At the midline, BMP inhibitors specify the paraxial mesoderm
Define a somite
A block of segmented tissue formed from the paraxial mesoderm on either side of the neural crest
What sequence does somitogenesis occur in?
Rostral to caudal (head to tail)
What are the 3 major components of a somite? And what do these components form?
- Sclerotome
- forms vertebrae and limbs (cartilage –> bone) - Myotome
- forms skeletal muscles of the back, and limbs - Dermatome
- forms the dermis of the back
What other process occurs at the same time as somitogenesis?
Neurulation
What day do somites start developing?
20
What day is somitogenesis complete on?
30
How many somites are formed at the end of somitogenesis? How many persist?
42-44 somite pairs are made. 37 persist
Where do somites form?
At the junction of retinoic acid (anterior end) and FGF8 (posterior). RA inhibits FGF8
What transcription factor is needed for somitogenesis?
Mesp (or mesp2 in humans/mice) which is mesodermal posterior. It is necessary for somite segmentation
What is the Notch pathway?
- Notch is a membrane bound ligand, when a signalling cell binds it activated the next steps
- a protease cuts a part of Notch off
- This piece of Notch binds to transcription factor (CSL) to allow transcription Hairy1 (Hes1)
Which side of the somite has Hairy1 expression?
Posterior due to the higher level of Notch
What type of feedback loop is the Notch pathway?
Negative
- Notch activates Mesp2, Mesp2 activates Epha4 anteriorly and Lunatic fringe, Lunatic fringe inhibits Notch via glycosylation
What is the possible function of Epha4?
This is an ephrin, and with its receptor it could potentially constitute a cut site for somite formation.
What does EPH-Ephrin signalling do?
Regulates epithelialization from mesenchymal cells. When Epha4 is up-regulated anteriorly, its binding partner is also up-regulated posteriorly (ephrinB2) which causes them to repel and segment.
What happens when there is a mutation in lunatic fringe?
The continuation of Notch signalling when Notch is supposed to be inhibited.
Which component of the somites is closest to the notochord? Which morphogen will this component be exposed to?
The sclerotome is closest. It will be exposed to more Shh to form vertebrae.
Which morphogen(s) is/are the primaxial myotome exposed to? (closer to the midline)
Shh and Wnt since it is in the middle of the neural tube and the notochord
Which morphogen(s) is/are the abaxial myotome exposed to? (farther from the midline)
Wnts from the epidermis. Also BMP4 and Fgfs from the lateral plate mesoderm
