Timing of Somite Creation

Intro

Mutation of notch delays the formation of somites, meaning that notch is required for the timing of somite formation, rather than the formation of somites. 

#1

Wnt and FGF, proteins secreted by cells in the tail, activate the notch pathway.

#2

When notch is active, it is cleaved at the plasma membrane and the cytoplasmic tail goes to the nucleus where it acts as a transcriptional regulator.

#3

In the nucleus, it activates a set of genes called Hes genes. Hes genes are an essential component of the developmental clock because of their oscillations.

#4

Once produced in the cytoplasm, the Hes protein moves into the nucleus to turn off its own transcription (oscillation peak).

#5

The existing Hes protein will be degraded over time due to normal mechanisms of protein homeostasis. Hes gene transcription will begin again (oscillation trough).

Note

If negative feedback is more delayed, it will lead to a decrease in the frequency of the peaks. This means the somite will be slightly longer. Oppositely, if you decrease the delay, the frequency of peaks will increase. This will create a shorter somite.

Conclusions

• Wnt and FGF maintain the oscillation of a transcriptional regulator within the presomitic mesoderm. The oscillation of the regulator is required to prevent the presomitic mesoderm from forming somites.

• As the source of Wnt and FGF moves further away, the oscillations begin to slow down and eventually arrest.

• The oscillating transcriptional regulator is arrested at either high expression or low expression.