Lecture 11

Question 1

Which axis is the first to be laid down during embryonic development

Answer 1

Anterior-posterior axis

Question 2

Explain the results of ectopic grafting of boundary cells

Answer 2

Somite boundary cells isolated from one embryo transplanted into another embryo is sufficient to induce the formation of a new boundary. Where you’d expect to see one somite you would now get two. This shows that boundary cells instruct cells that are anterior to it to form a boundary

Question 3

Which mesodermal tissue gives rise to the somites

Answer 3

Paraxial mesoderm

Question 4

Which germ layer forms at the primitive streak during gastrulation

Answer 4

Mesoderm

Question 5

What five factors must cells in the paraxial mesoderm be able to respond to

Answer 5

Positional information, mechanisms that coordinate left and right, anterior and posterior boundary formation and the formation of the cleft

Question 6

What is meant by the determination front

Answer 6

Wavefront that travels from the anterior part of the presomitic mesoderm towards the posterior embryo

Question 7

What determines the adoption of different mesodermal fates in the developing embryo

Answer 7

Where the cells ingress along the anterior-posterior axis into the primitive streak

Question 8

How do RA and FGF8 interact to regulate expression of transcription factor(s) involved in somite boundary formation

Answer 8

RA activates Mesp2 expression whilst FGF8 inhibits it. Mesp2 expression in turn blocks local Notch signalling. Lower Notch signalling on one side of the border results in high notch signalling in adjacent cells on the other side of the boundary.

Question 9

What transcription factor do RA and FGF8 regulate the expression of

Answer 9

Mesp2

Question 10

What model describes the periodicity of somite formation and how is this achieved

Answer 10

Clock and wavefront model. The clock explains the temporal component whilst the wavefront provides spatial information to drive somite formation. Where cells hit the travelling wavefront an abrupt change of property leads to the decision to form somites

Question 11

The pre-somitic mesoderm is unsegmented, T or F

Answer 11

T

Question 12

Describe the rough structure of the somites viewed as a horizontal cross section

Answer 12

The somites show a clear metameric structure with a clear repeating pattern and defined anterior and posterior boundaries

Question 13

How do the number of somites relate to segmentation in vertebrates such as humans

Answer 13

Somite number dictates the number of vertebrae

Question 14

The axial mesoderm is one of the mesodermal tissues formed by the ingression of cell into the primitive streak, what two subtypes of mesoderm does it give rise to and where

Answer 14

Prechordal mesoderm (anteriorly) and the notochord (posteriorly)

Question 15

Cells that ingress posteriorly to the paraxial mesoderm give rise to which tissue

Answer 15

Intermediate mesoderm

Question 16

RA and FGF8 agonise eachother, T or F

Answer 16

F – they antagonise each other

Question 17

What family of genes were discovered to be expressed at the somite boundaries

Answer 17

Notch family genes. They are selectively expressed in the anterior or posterior part of the somite

Question 18

Explain the results of forced lunatic fringe expression in the paraxial mesoderm and the significance of this

Answer 18

Lunatic fringe is a gene that blocks notch activity and thus forced expression results in an inhibition of notch signalling. This results in the formation of a new boundary and hence an additional somite

Question 19

The number of somites is fixed for any given species and the timing of somite formation remains constant, T or F

Answer 19

F – whilst the number of somites does differ between species, so too does the timing of somite generation

Question 20

Explain how RA and FGF8 interact to dictate determination front positioning

Answer 20

High levels of FGF8 result in high levels of Cyp26 which inhibits RA synthesis. High levels of FGF8 also inhibit the production of the Rhald2 enzyme that is normally required for RA synthesis

Question 21

Explain how a molecular oscillator drives mesodermal segmentation in chick embryos

Answer 21

In the embryo levels of the helix-loop-helix transcription factor C-hairy was found to fluctuate at different embryonic stages. Later genes were discovered that regulate the timing of this clock oscillation and are members of the notch, wnt or FGF signalling pathways

Question 22

Somites are the earliest evidence of segmentation in vertebrates, T or F

Answer 22

T

Question 23

Give an example of a human disease that proves a role of notch signalling in mesodermal segmentation

Answer 23

Jarcho Lewin syndrome causes spondylocostal dysplasia due to problems with the segmentation of the axial skeleton. This occurs due to a mutation in the delta 3 ligand that alters notch signalling and problems with somite segmentation

Question 24

List the structures that the paraxial mesoderm give rise to

Answer 24

Axial skeleton, heart, somites, cartilage and tendons

Question 25

How many components is the lateral mesoderm divided into and what do these divisions give rise to

Answer 25

The lateral mesoderm divides into 3 components, two of which give rise to the circulatory system and the other which contributes to extraembryonic structures and limb bones

Question 26

How does the determination front dictate somitigenesis

Answer 26

When the cells of the paraxial mesoderm encounter oscillations from the molecular clock an abrupt change determines their formation of the next somite pair

Question 27

What are the downstream effects of opposing notch signalling in cells either side of the boundary

Answer 27

High notch acitivity in one side and low activity in the cells opposite leads to formation of the somite boundary. The boundary itself forms from physical formation of cleft within the mesenchymal tissue. Downstream extensive changes in cell morphology and adhesion leads to creation of this cleft and is mediated by ephs and ephrins

Question 28

What structure separates the left and right somites

Answer 28

Spinal cord

Question 29

The formation of somites occurs in a sequential manner on both sides with the size of somites being preserved throughout, T or F

Answer 29

T

Question 30

Alike the axial mesoderm, the posterior paraxial mesoderm is also subdivided, what are these subdivisions

Answer 30

Unsegmented posterior paraxial mesoderm and the segmented posterior paraxial mesoderm that give rise to somites

Question 31

How many somites are present in humans and how does this relate to their segmentation

Answer 31

The human embryo has between 38 and 44 somites, this correlates to the 33 vertebrae which we are born with

Question 32

Explain how the determination front is positioned

Answer 32

The determination front is determined at the interface of two opposing gradients. Retinoid acid which is high anteriorly and fibroblast growth factor 8 which is high posteriorly. When these gradients are equal the determination front forms.

Question 33

What structures do the intermediate mesoderm give rise to

Answer 33

Kidneys and gonads

Question 34

Where is retinoic acid produced to dictate determination front positioning

Answer 34

Somites

Question 35

The more posterior a cell ingresses into the primitive streak, the more posterior the mesoderm it will give rise to will be, T or F

Answer 35

F – more posterior ingress, the more lateral the mesoderm

Question 36

Put these different mesodermal tissue types in order from most anterior to most posterior. Intermediate mesoderm, axial mesoderm, lateral mesoderm, paraxial mesoderm

Answer 36

Axial mesoderm, paraxial mesoderm, intermediate mesoderm, lateral mesoderm

Question 37

What aspect of the paraxial mesoderm determines somite boundary formation

Answer 37

Position of the somite minus II (S-II)

Question 38

What experimental method lead to the identification of the origin of mesodermal tissue development

Answer 38

Lineage tracing