Mesoderm segementation Flashcards
How does paraxial mesoderm form in vertebrates
Forms in a continuous manner until the proper somite number is formed
What type of mesoderm prefigures the future segmentation of somitess?
non-segmented presomitic mesoderm
How often do somites form in chicks?
One pair every 90 minutes
What must cells of paraxial mesoderm respond to to become somites
1) positional information - at anterior it will form a somite
2) Mechanism to co-ordinate between left and right parts of paraxial mesoderm
3) Mechanism to generate anterior boundary/ posterior boundary
4) Formation of a cleft between the somites
How is the periodicity of somite formation established?
The clock and wavefront model
Clock - posterior paraxial mesoderm has molecular oscillations that dictate the periodicity of somites
Wavefront - Where these cells hit the travelling wavefront an abrupt change of properties occurs leading to the decision to form somites
What is the evidence for the molecular oscillator
Expression pattern of C-hairy
Was found to be expressed in the paraxial mesoderm but expression was different in embryos of the same stage
So they bisected embryos down the middle and fixed one half whilst allowing the other half to develop further in culture for differing amounts of time.
The half in culture would change its expression of C-hairy over time depending on how long it was kept in culture.
Graphical representation of this revealed an oscillation of expression
How does the time of the oscillation affect somite formation
One full oscillation depicts one pair of somites formation
What is the determination front
The timing at which the next prospective somites are going to be forming
How was the chick embryo used to induce somite boundary formation
Transplantation of prospective somite boundary region into a non-boundary region, creating a new boundary
Boundary cells instruct cells that are anterior to form a boundary, created 2 somites where there should only be one
What are the molecular characteristics of somite boundaries
Notch family genes are expressed at the same somite boundary
Selectively expressed in A or P part of the somite
This implies a role in border formation
What is the role of lunatic fringe and how was this shown
Lunatic fringe blocks notch signalling activity
Forced expression of the gene results in a new boundary and an additional somite
How are mutations in humans affecting notch signalling characterised
Strong defects in segmentation of the axial skeleton
How do the cells know that they must initiate the boundary formation
The determination front is positioned at the interface of two opposing gradients
1) RA produced by somites - decreases going posteriorly
2) FGF8 produced at the primitive streak and the posterior mesoderm decreasing anteriorly
How do FGF and RA regulate eachothers expression
Mutual inhibition
FGF8 expression induces high expression Cyp26 which inhibits RA production
FGF8 also blocks synthesis of Raldh2 - an enzyme required for RA synthesis
RA inhibits FGF8 synthesis
How do FGF8 and RA control the determination front
FGF8 and RA control the expression of Mesp2
RA induces its expression whereas FGF8 inhibits its expression
Masp2 expression blocks local notch signalling
Lower notch signalling on one side of the border results in high notch signalling in the adjacent cells on the other side of the boundary
