Somitogenesis

Question 1

What is the wavefront?

Answer 1

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.

Question 2

What is the clock?

Answer 2

The cyclic activation of Wnt signalling as well as downstream genes. (This sets location and timing for somite separation)

Question 3

What do somites form from?

Answer 3

The paraxial mesoderm

Question 4

Where is BMP activity the lowest in the mesoderm?

Answer 4

At the midline, BMP inhibitors specify the paraxial mesoderm

Question 5

Define a somite

Answer 5

A block of segmented tissue formed from the paraxial mesoderm on either side of the neural crest

Question 6

What sequence does somitogenesis occur in?

Answer 6

Rostral to caudal (head to tail)

Question 7

What are the 3 major components of a somite? And what do these components form?

Answer 7

1. Sclerotome
   - forms vertebrae and limbs (cartilage –> bone)
2. Myotome
   - forms skeletal muscles of the back, and limbs
3. Dermatome
   - forms the dermis of the back

Question 8

What other process occurs at the same time as somitogenesis?

Answer 8

Neurulation

Question 9

What day do somites start developing?

Answer 9

20

Question 10

What day is somitogenesis complete on?

Answer 10

30

Question 11

How many somites are formed at the end of somitogenesis? How many persist?

Answer 11

42-44 somite pairs are made. 37 persist

Question 12

Where do somites form?

Answer 12

At the junction of retinoic acid (anterior end) and FGF8 (posterior). RA inhibits FGF8

Question 13

What transcription factor is needed for somitogenesis?

Answer 13

Mesp (or mesp2 in humans/mice) which is mesodermal posterior. It is necessary for somite segmentation

Question 14

What is the Notch pathway?

Answer 14

1. Notch is a membrane bound ligand, when a signalling cell binds it activated the next steps
2. a protease cuts a part of Notch off
3. This piece of Notch binds to transcription factor (CSL) to allow transcription Hairy1 (Hes1)

Question 15

Which side of the somite has Hairy1 expression?

Answer 15

Posterior due to the higher level of Notch

Question 16

What type of feedback loop is the Notch pathway?

Answer 16

Negative
- Notch activates Mesp2, Mesp2 activates Epha4 anteriorly and Lunatic fringe, Lunatic fringe inhibits Notch via glycosylation

Question 17

What is the possible function of Epha4?

Answer 17

This is an ephrin, and with its receptor it could potentially constitute a cut site for somite formation.

Question 18

What does EPH-Ephrin signalling do?

Answer 18

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.

Question 19

What happens when there is a mutation in lunatic fringe?

Answer 19

The continuation of Notch signalling when Notch is supposed to be inhibited.

Question 20

Which component of the somites is closest to the notochord? Which morphogen will this component be exposed to?

Answer 20

The sclerotome is closest. It will be exposed to more Shh to form vertebrae.

Question 21

Which morphogen(s) is/are the primaxial myotome exposed to? (closer to the midline)

Answer 21

Shh and Wnt since it is in the middle of the neural tube and the notochord

Question 22

Which morphogen(s) is/are the abaxial myotome exposed to? (farther from the midline)

Answer 22

Wnts from the epidermis. Also BMP4 and Fgfs from the lateral plate mesoderm