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Neuroscience Y2S1 > Building Brains 6 - Vertebrates > Flashcards

Building Brains 6 - Vertebrates Flashcards

1
Q

Name the zone of the neural tube in the vertebrate embryo which lies closest to the lumen, and contains the proliferating epithelium. (1)

A

Ventricular zone

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2
Q

In the DV axis of the vertebrate embryo spinal cord, distinct cell types arise from corresponding domains of proliferating epithelium.

How are these domains distinguished from one another? (1)

A

Expression of different transcription factors

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3
Q

Name all of the progenitor domains in the DV axis of the vertebrate embryo spinal cord which give rise to specific neurones. (lots of marks)

A

dl1
dl2
dl3
dl4
dl5
dl6
V0
V1
V2
MN
V3

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4
Q

Name the structures which lie…

a) most dorsal in the neural tube
b) most ventral in the neural tube

(2)

A

a) roof plate
b) floor plate

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5
Q

True or false? (1)

The floor plate is an epithelial structure in the dorsal neural tube.

A

False - the floor plate is an epithelial structure in the VENTRAL neural tube

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6
Q

Name the structure in the vertebrate embryo which induces development of the floor plate of the neural tube. (1)

A

Notochord

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7
Q

True or false? (1)

In the neural tube of the vertebrate embryo, the notochord and floor plate induce the formation of ventral structures, such as sensory neurones.

A

False - change sensory neurones to motor neurones

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8
Q

Briefly describe an experiment where the sufficiency of the notochord to induce ventral fates in the vertebrate embryo neural tube could be tested.
Describe the expected results. (3)

A
  • Transplant an extra notochord in different area
  • Should see extra ventral structures

eg. floor plate and motor neurone pools

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9
Q

Briefly describe an experiment where the necessity of the notochord to induce ventral fates in the vertebrate embryo neural tube could be tested.
Describe the expected results. (3)

A
  • Ablation of notochord
  • Would lead to loss of floor plate and motor neurones
  • Also, dorsal markers would extend ventrally
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10
Q

Name the molecule in the vertebrate embryo which patterns the ventral part of the neural tube. (1)

A

Sonic hedgehog

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11
Q

True or false? (1)

In the vertebrate embryo, sonic hedgehog is a morphogen and a transcription factor.

A

False - it is a morphogen, but is a secreted peptide, not a transcription factor

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12
Q

Describe the Shh signalling pathway. (3)

A
  • Shh binds to patched
  • Patched activated smoothened
  • Smoothened allows GLI to acts as a transcriptional activator instead of a transcriptional repressor
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13
Q

Which structure/s in the vertebrate embryo express/es Shh protein?

A

Notochord and floor plate

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14
Q

Shh affects homeodomain proteins (TFs) in the vertebrate embryo neural tube, in order to create distinct domains.

There are two classes of homeodomain proteins which respond differently to Shh.

Name these two classes and state how they respond to Shh. (4)

A

Class I proteins repressed by Shh

Class II proteins activated by Shh

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15
Q

True or false? (1)

All class I proteins in the vertebrate embryo neural tube are repressed equally by Shh, and all class II proteins are activated equally.

A

False - proteins show varying strengths of response to Shh to create variable expression in the DV axis

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16
Q

True or false? (1)

In the DV axis of the vertebrate embryo neural tube, each ventral domain expresses a unique transcription factor (under the control of Shh) to distinguish it from other domains.

A

False - different combinations of transcription factors are expressed in each domain

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17
Q

In the vertebrate embryo neural tube DV axis, class I transcription factors and class II transcription factors (controlled by Shh) sometimes share a boundary between different domains.

How do these TFs ensure that the boundary is sharp? (1)

A

Mutual inhibition

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18
Q

Describe an experiment that could be carried out to test the mutual inhibition of class I and class II transcription factors in the vertebrate embryo ventral neural tube. (2)

A
  • Overexpress one TF
  • Use colocalisation to see if these TFs are able to be expressed together or if they are inhibited
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19
Q

Describe how in ovo electroporation can be used to force a chick embryo to overexpress certain transcription factors. (4)

A
  • Cells pulsed with electric current
  • This forces them to take up molecules (eg. DNA/RNA) which have been injected into the organism
  • Molecule will move to area of electric current to which they are attracted (eg. -ve charged molecule moves towards positive current)
  • Can cause over/under/mis-expression of specific genes
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20
Q

Describe what you would expect to happen if vertebrate embryo neural tube cells which are from the dorsal region are cultured which Shh? (1)

A

They will take on a ventral fate

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21
Q

Name the class I transcription factors which are inhibited by Shh in the ventral part of the vertebrate embryo neural tube. (5)

A

Pax7

Pax6

Dbx1

Dbx2

Irx3

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22
Q

Name the class II transcription factors which are activated by Shh in the ventral part of the vertebrate embryo neural tube. (2)

A

Nkx6.1

Nkx2.2

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23
Q

Name the part of the vertebrate embryo which induces formation of the roof plate. (1)

A

Dorsal ectoderm which has healed over the neural tube.

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24
Q

Name the molecule/s which is/are produced by the dorsal ectoderm and roof plate in the vertebrate embryo to induce dorsal fates in the neural tube.

A

BMP

Along with other members of the TGF-b family

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25
Q

Name the family of molecules which BMP belongs to. (1)

A

TGF-b superfamily

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26
Q

True or false? (1)

BMPs released from the dorsal ectoderm and floor plate in the vertebrate embryo form a concentration gradient in order to induce different dorsal fates in the neural tube.

A

False - change floor plate to roof plate

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27
Q

Name two structures in the vertebrate embryo which release BMPs, along with other members of the TGF-b family, to pattern the dorsal part of the neural tube. (2)

A
  • Dorsal ectoderm
  • Roof plate
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28
Q

Apart from Shh, BMP, and members of the TGFb family, name another molecule which may be involved in patterning the vertebrate embryo neural tube in the DV axis. (1)

A

Wnt

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29
Q

Describe ‘specification’, when referring to levels of cellular commitment. (2)

A

The cell is capable of differentiating autonomously in a neutral environment.

This stage can be reversed.

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30
Q

Describe ‘determination’, when referring to levels of cellular commitment. (2)

A

The cell will retain its fate when place into a different environment of the embryo (which may promote other fates).

This stage is irreversible and the cell is now committed to a particular fate.

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31
Q

Describe one difference in the lumen of the neural tube between the cranial and caudal ends of the vertebrate embryo. (2)

A

CRANIAL:
- Cells secrete fluid into lumen to create brain vesicles

CAUDAL:
- Lumen remains very narrow with no fluid secretion

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32
Q

Describe the protein products which are produced due to the expression of Hox genes. (2)

A

Transcription factors

which contain a homeodomain that interacts with DNA.

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33
Q

What is the role of Hox genes/transcription factors in the vertebrate embryo? (3)

A

Activate programs of gene expression

along AP axis

for all tissues in the embryo, not just neural tissues.

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34
Q

Although Hox genes have been highly conserved between organisms (eg. flies and humans), the Hox genes expressed in higher organisms are different to those expressed in Drosophila.

Explain how and why the Hox code is different. (3)

A

As vertebrates have evolved the Hox genes have duplicated

so more Hox genes present in vertebrates

to produce a much more complex AP pattern.

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35
Q

Describe the importance of the Hox genes being expressed in a specific order on the chromosome during embryonic development. (2)

A
  • Hox genes expressed on chromosome in the order that they are expressed on AP axis
  • This has been conserved between organisms so the same Hox gene which forms the head region in drosophila will also form the head region in vertebrates
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36
Q

Describe the organisation of the embryonic rhombencephalon in the AP axis. (1)

A

Split into rhombomeres

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37
Q

Describe what would happen in the vertebrate embryo if two rhombomeres expressed the same Hox genes. (1)

A

These rhombomeres would have the same structure and function

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38
Q

Describe what is meant by the following sentence:

‘Hox genes exhibit nested domains of expression in the vertebrate embryo.’

(3)

A

Hox genes have overlapping domains of expression.

More Hox genes are turned on moving posteriorly in the embryo.

Moving posteriorly, the more anterior genes fade out and the ‘newly expressed’ genes become more dominant.

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39
Q

Describe the synthesis and degradation of RA in the vertebrate embryo. (3)

A

RA synthesised from vitamin A.

By Raldh enzymes expressed by mesoderm.

Then degraded anteriorly by enzymes (eg. Cyp26a1).

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40
Q

How is retinoic acid able to influence Hox gene expression in the vertebrate embryo? (1)

A

Hox gene promotors may express retinoic acid response elements (RARE).

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41
Q

Complete the sentence. (1)

In the vertebrate embryo, the peripheral nervous system is derived from …………………………..

A

The neural crest / neural crest cells

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42
Q

Which part of the early vertebrate embryo (after gastrulation but before neurulation has occurred) goes on to form the neural crest? (1)

A

Neural plate border

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43
Q

In the early vertebrate embryo, is the neural crest located ventrally or dorsally in the neural tube? (1)

A

Dorsally

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44
Q

True or false? (1)

As in the CNS, the PNS develops from anterior to posterior in the vertebrate embryo.

A

True

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45
Q

Give five cell types in the vertebrate embryo/adult that are derived from the neural crest. (5)

A
  • Neurones
  • Glial cells
  • Pigment cells (melanocytes)
  • Endocrine cells (chromaffin cells)
  • Mesenchymal cells (osteocytes)
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46
Q

What do studies show happens if the dorsal neural tube (ie. the neural crest) is ablated in the vertebrate embryo? (1)

A

The neural crest regenerates

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47
Q

Give three molecules which may be early markers of the neural crest cells in the vertebrate embryo.

Where are these molecules expressed? (4)

A
  • Pax7
  • Sox10
  • HNK1

Expressed at the neural plate border.

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48
Q

What type of molecule is Pax7? (1)

A

Transcription factor

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49
Q

Describe a difference in the expression of Pax7 and Sox10 in the neural crest / PNS of the vertebrate embryo. (2)

A

Pax7 expressed earlier and switched off as neural crest cells migrate away from neural tube.

Sox10 expressed later and doesn’t switch off as cells migrate.

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50
Q

Name two signalling molecules that can induce neural crest, depending on their timing and exposure in the vertebrate embryo. (2)

A
  • Wnt
  • BMP
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51
Q

Describe the temporal relationship between wnt and BMP which is required to induce neural crest in the vertebrate embryo. (2)

A

Wnt induces BMP

and then remains switched on.

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52
Q

True or false? (1)

Later in vertebrate embryonic development, BMPs alone can induce neural crest, without involvement from Wnt.

A

True

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53
Q

Describe what you would expect to happen if you cultured ventral neural tube cells from the vertebrate embryo with a sample of ectoderm.
Why would this happen? (2)

A

Cells would become neural crest

because ectoderm produces BMPs.

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54
Q

Describe what you would expect to happen if you cultured ventral neural tube cells from the vertebrate embryo with added BMP4 and BMP7. (1)

A

Neural crest would be produced.

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55
Q

How might studying neural crest cell migration be relevant in clinical situations? (1)

A

Neural crest cell migration may also be applicable to cancer metastasis.

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56
Q

Name a gene in the vertebrate embryo which is essential to allow neural crest cells to migrate.
What family is this gene a member of? (1)

A

Slug (snail in mice)

Member of snail family

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57
Q

What type of protein does the slug gene encode in the vertebrate embryo? (1)

A

Zinc-finger transcription factor

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58
Q

Describe how expression of the slug gene in the vertebrate embryo allows neural crest cells to migrate. (1)

A

Inhibits N-cadherin

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59
Q

Name a cadherin in the vertebrate embryo which has to be active to allow neural crest cell migration. (1)

A

Cadherin-7

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60
Q

Describe what you would expect to happen if antisense oligonucleotides against slug were injected into a vertebrate embryo. (1)

A

Neural crest cells would not be able to migrate.

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61
Q

True or false? (1)

The mechanism of inhibiting cadherin-7 and activating N-cadherin to allow neural crest cell migration can be applied to all vertebrates.

A

False:

  • It may not happen in mammals
  • N-cadherin is inhibited and cadherin-7 is activated
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62
Q

Briefly describe the two possible migratory routes that neural crest cells can take.
Give an example of the ‘types/fates’ of neural crest cells that take each route. (4)

A
  • Through somites (eg. dorsal root ganglia)
  • Just underneath ectoderm (eg. melanocytes)
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63
Q

Describe the results of an experiment where:

a) the neural tube
b) the somites

in the vertebrate embryo are rotated to study the route that neural crest cells take during migration. (2)

A

Neural crest cells will ALWAYS migrate through the anterior section of somite (or the section that was originally anterior).

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64
Q

What can be deduced from the finding that neural crest cells always migrate through the anterior portion of somites, even if the somites or neural crest are rotated? (2)

A

Somite tissue dictates neural crest migration,

posterior section produces a repulsive signal.

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65
Q

In which embryonic animal model would experiments be best performed which involve rotating either the neural tube or the somites to study neural crest cell migration? (1)

A

Chick

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66
Q

In which region of the vertebrate embryo may neural crest cells be able to make bone and muscle?
Name two transcription factors needed for this. (3)

A

Cranial region

Sox8
Sox9

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67
Q

In what type of embryonic animal model are experiments typically performed regarding neural crest cell fate? (1)

A

Quail/chick chimeras

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68
Q

In general, are neural crest cells specified before or after migration in the vertebrate embryo?

Describe how/when the neural crest cells acquire their fate. (4)

A

Cells acquire fate at various times.

Neural crest cells appear to be a mixture of cells at various stages of commitment to different fates.

Some cells are still able to acquire all fates and some are more restricted.

As cells migrate, if they arrive in an appropriate environment to develop one of their specified fates, they do so, and if not, they die.

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69
Q

What is a placode, and what do placodes turn into in the vertebrate embryo/adult? (3)

A

Specialised regions of the cranial neuroectoderm

which form special sense organs and some sensory neurones in the head.

But some placodes from non-neural ectoderm can form hair follicles, feathers, and teeth.

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70
Q

Give four genes/molecules that establish neural competence to neural crest cells. (4)

A
  • BMP
  • FGF
  • Wnt
  • Pax7
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71
Q

Give three genes/molecules which play a role in delamination and migration of neural crest cells. (3)

A
  • Snail/slug
  • FoxD3
  • Sox10
72
Q

Give a potential role of Sox10 in the delamination and migration of neural crest cells in the vertebrate embryo. (1)

A

Activates cadherin-7

73
Q

Describe what is meant by the following sentence. (3)

To initiate neural crest cell delamination and migration in the vertebrate embryo, there must be a switch from type I to type II cadherins.

A

N-cadherin is type I

Cadherin-7 is type II

Switch from N-cadherin to cadherin-7 essential for migration.

74
Q

True or false? (1)

The methods that axons use to navigate to their target in the vertebrate embryo are thought to be the same as glia, dendrite, and neural crest path finding.

A

True

75
Q

Complete the sentence regarding vertebrate embryos. (1)

The …………………. is the part at the end of the neurite which facilitates extension of the neurite.

A

growth cone

76
Q

What are microspikes, in relation to growth cones? (1)

A

Tiny projections which come off the filopodia.

77
Q

Describe the cytoskeleton of the embryonic axon and growth cone. (3)

A

Axon formed of microtubules

Growth cone contains actin network

Actin bundles and a few microtubules extend into filopodia

78
Q

What is the name given to microtubules which extend into the filopodia of the growth cone? (1)

A

Pioneer microtubules

79
Q

How are pioneer microtubules able to drive axon growth at the tip of the growth cone? (1)

A

Contain kinesin on their tips

80
Q

True or false? (1)

The growth cone is a highly-active structure, meaning that some essential molecules such as DNA and proteins (tubulin) are constantly being transported to the growth cone.

A

False - molecules are STORED in the growth cone, and it is RNA (DNA stays in nucleus)

81
Q

Name the small protein molecules which make microtubules. (1)

A

Tubulin

82
Q

Describe the arrangement of microtubules within the vertebrate embryonic axon. (2)

A
  • Microtubules laid down with plus ends (rapidly growing ends) pointed towards tip
  • Microtubules cross-linked by microtubule-associated proteins (MAPs)
83
Q

Give two examples of microtubule-associated proteins found in the embryonic axon, and describe their function. (2)

A
  • Examples include Tau and MAP1/MAP2 families
  • MAPs help transport molecules to the growth cone from the cell body
84
Q

Describe the location and function of the actin meshwork in an embryonic axon. (2)

A
  • Located just underneath plasma membrane
  • Provides shape and stability
85
Q

Name the proposed mechanism by which a growth cone can extend and elongate the axon in the vertebrate embryo. (1)

A

Molecular clutch

86
Q

Briefly describe the molecular clutch hypothesis of axon/growth cone growth in the vertebrate embryo. (4)

A

Clutch not engaged = membrane anchored to ECM but actin cytoskeleton is not

When new actin molecules added, retrograde flow occurs as new actin cannot protrude

Clutch engaged = both membrane and cytoskeleton anchored to ECM

Addition of new actin cannot cause retrograde flow so new actin protrudes and causes growth

87
Q

Describe why a balance must be established between a growth cone making and breaking connections with the ECM in order for the growth cone to cause axon elongation. (2)

A
  • As leading edge advances forwards (makes connections),
  • following edge must unstick to allow whole structure to move.

(As front sticks, back has to unstick)

88
Q

Name the individual molecules which stick together to form an actin filament. (1)

A

Microfilament

89
Q

Describe the response of a growth cone in the vertebrate embryo when it meets a repulsive guidance cue. (2)

A
  • Growth cone collapses
  • Then the growth cone puts out new processes to attempt to grow again
90
Q

Describe the response of a growth cone in the vertebrate embryo when it meets an attractive guidance cue. (1)

A

Activation of actin and tubulin outgrowth mechanisms.

91
Q

True or false? (1)

As an axon begins to extend towards its target, it mainly responds to diffusible cues, and contact cues become more relevant as the axon gets closer to its target.

A

False - first responds to contact cues, then diffusible cues close to target

92
Q

Name the main signalling pathway within the axonal growth cone which leads to either collapse or extension after a guidance cue has been detected. (1)

A

Rac-Rho System

93
Q

Describe how the Rac-Rho system responds when an attractive guidance cue binds to the axonal growth cone. (2)

A

Rac activated.

Rac inhibits Rho and stimulates growth via the actin cytoskeleton.

94
Q

Describe how the Rac-Rho system responds when a repulsive guidance cue binds to the axonal growth cone. (2)

A

Rho activated

Rho inhibits Rac and inhibits growth of actin cytoskeleton.

95
Q

What types of molecules are Rac and Rho? (1)

A

G-proteins

96
Q

How are Rac and Rho activated/inactivated in the axonal growth cone? (1)

A

Via interaction with GDP/GTP

97
Q

Describe how different neurites are able to respond differently to the same external guidance cues. (1)

A

Different intra- and extra-cellular machinery

(eg. receptors and signalling pathways)

98
Q

True or false? Give an explanation. (1)

Some aspects of neurite outgrowth can be cell autonomous and do not rely on external cues.

A

True - given types of neurones can produce specific general morphologies (eg. motor neurone with one axon or purkinje cell with many dendrites)

99
Q

Are axons organised before outgrowth, or do they become organised once they have found a target? (1)

A

Tend to be organised before outgrowth (have specific targets which they will grow towards)

100
Q

Give three general pathways that axons might follow as they first migrate (pretty non-specifically) to their target. (3)

A
  • Along blood vessels
  • glial tracts
  • Tissue borders
101
Q

True or false? (1)

Studies show that axons will always grow towards their specific intended target, but if this target is out of range the axon will die.

A

False - Axons will grow towards their specific target, but if that target is not in range they have the ability to find a similar type of target to innervate

102
Q

True or false? (1)

Vertebrate embryos tend to use the same axon guidance molecules found in invertebrate embryos.

A

True

103
Q

Name two types of molecules involved in cell-cell adhesion during axon pathfinding in the vertebrate embryo. (2)

A

Cadherins

Cell adhesion molecules (CAMs)

104
Q

Name three types of molecules involved in cell-ECM adhesion during axon pathfinding in the vertebrate embryo. (3)

A
  • Integrins
  • Laminin
  • Fibronectin
105
Q

Give three examples of cell-attached, positive axon guidance cues in the vertebrate embryo. (3)

A
  • CAMs
  • Cadherins
  • Integrins
106
Q

Give an example of a secreted, positive axon guidance cue in the vertebrate embryo. (1)

A

Netrin I

107
Q

Give two examples of secreted, negative axon guidance cues in the vertebrate embryo. (2)

A
  • Netrins
  • Semaphorins
108
Q

Give one example of a cell-attached, negative axon guidance cue in the vertebrate embryo. (1)

A

Semaphorin I

109
Q

Describe whether cadherins and CAMs are homophilic or heterophilic. (2)

A

Cadherins are homophilic

CAMs can be homophilic or heterophilic

110
Q

Describe whether cadherins and CAMs are calcium-dependent or calcium-independent. (2)

A

Cadherins are calcium-dependent

CAMs are calcium-independent

111
Q

Give an example of a cadherin involved in axon guidance. (1)

A

N-Cadherin

112
Q

Give an example of a CAM involved in axon guidance. (1)

A

N-CAM

113
Q

Describe how integrins and laminins/fibronectins interact to form cell-ECM connections during axon guidance. (2)

A

Integrins attached to cells and extend into ECM

Integrins on cells bind to laminin/fibronectin in ECM

114
Q

In the vertebrate embryo, the floor plate expresses netrin-1.

Describe the response of:

a) commissural/sensory neurones
b) motor neurones

to the floor plate. (1)

A

Sensory neurones attracted to floor plate.

Motor neurones repelled from floor plate.

115
Q

Describe the response of commissural axons which are grown in culture with:

a) floor plate
b) roof plate
c) fibroblasts expressing Netrin-1

(3)

A

a) axons attracted to floor plate

b) axons not attracted to roof plate

c) axons attracted to fibroblasts

116
Q

Give an example of how 2 different types of neurone can respond differently to a group of semaphorin-3 secreting cells. (2)

A
  • Mechanoreceptor neurones will be repelled
  • NT-3 responsive neurones will be attracted
117
Q

True or false? (1)

Different regions of a cell (eg. dendrites and neurones) can have different responses to the same guidance cue.

A

True

118
Q

Describe and explain the results of an experiment which tested the effect of semaphorin 3a on the dendrites/axon of the same cell.
How is this affected by cGMP? (5)

A

Dendrites grow towards SEMA-3A

because they express cGMP.

Axons grow away from SEMA-3A

because they do not express cGMP.

Guanylyl cyclase ‘cap’ seen where dendrite forms and throughout dendrite.

119
Q

Describe how commissural axons in the vertebrate embryo spinal cord have to change their response to guidance cues as they cross the midline. (3)

A
  • Initial attraction to floor plate
  • Then repulsion from floor plate
  • Then direction change to travel up spinal cord
120
Q

An ‘open book’ explant was performed, where the neural tube from a vertebrate embryo was unrolled (so floor plate was located in the middle of the tissue strip), and commissural axon growth was observed.

What would happen if:

a) nothing was changed
b) ectopic floor plate was added before normal floor plate
c) ectopic floor plate was added after normal floor plate
d) normal floor plate moved to a point further along the tissue strip

What does this tell us about the changing response of commissural fibres to axon guidance cues? (5)

A

a) axons travel through floor plate then carry on away from it like usual

b) axons travel to ectopic floor plate and do not continue growth towards the normal floor plate

c) axons travel through normal floor plate and ignore ectopic floor plate

d) axons travel to floor plate despite its change of location

This tells us that axons are attracted to the floor plate, but once they have crossed, they are repelled by floor plate.

121
Q

Describe how vertebrate embryo commissural axons are attracted to the midline floor plate. (2)

A

Netrin secreted by midline.

Axons express DCC receptor.

122
Q

Name the ligand and receptor which mediate the repulsive properties of the midline floor plate to commissural axons in the vertebrate embryo. (2)

A

Slit and robo

123
Q

If netrin is not expressed by the midline floor plate in the vertebrate embryo, some commissural axons will still grow towards the floor plate.
How is this possible? (2)

A
  • Shh attraction
  • BMP repulsion
124
Q

Name the molecule (in drosophila, but which may also apply to vertebrates) which alters expression of robo in commissural axons as they cross the midline floor plate. (1)

A

Comm

125
Q

Name the cell adhesion molecule which is expressed by longitudinal fascicles travelling in the vertebrate embryo spinal cord, which allows commissural axons to join once they have crossed the midline. (1)

A

Fasciclin II

126
Q

There are three main fascicles travelling longitudinally in the vertebrate embryo spinal cord to the brain (medial, intermediate, and lateral).

Commissural axons expressing only robo1 will join which fascicle after they have crossed the midline floor plate? (1)

A

Medial

127
Q

There are three main fascicles travelling longitudinally in the vertebrate embryo spinal cord to the brain (medial, intermediate, and lateral).

Commissural axons expressing robo1 and robo3 will join which fascicle after they have crossed the midline floor plate? (1)

A

Intermediate

128
Q

There are three main fascicles travelling longitudinally in the vertebrate embryo spinal cord to the brain (medial, intermediate, and lateral).

Commissural axons expressing robo1, robo2, and robo3 will join which fascicle after they have crossed the midline floor plate? (1)

A

Lateral

129
Q

Describe how the robo receptors that a commissural axon expresses helps determine which fascicle (medial, intermediate, lateral) the axon will join once it has crossed the midline of the vertebrate embryo. (3)

A

The more robo receptors (ie, robo1/robo2/robo3 or a mixture) a neurone expresses

the more sensitive it will be to midline slit repulsion

and the further it will grow away from the midline.

ie. more robo = lateral fascicle

130
Q

Describe what is meant by the ‘retinotectal map’. (2)

A

The process by which information from the retina is mapped onto the visual cortex

in a spatially-organised fashion.

131
Q

Complete the sentence regarding the formation of the vertebrate retinotectal map. (2)

Neurones grow along the surface of the retina to the exit point, where ………………. promotes migration and fasciculation to form the …………………..

A

N-CAM

Optic Nerve

132
Q

Complete the sentence regarding the formation of the vertebrate retinotectal map. (2)

Where the optic nerve exits the retina, the combination of ……………….. and extracellular ………………. repels axons and stimulates them to grow into the brain.

A

Netrin-1

Laminin

133
Q

Complete the sentence regarding the formation of the vertebrate retinotectal map. (2)

At the optic chiasm, ………………… on brain cells and ……………… receptors on axons allow some axons to cross and some to remain ipsilateral.

A

Ephrins

Eph

134
Q

Complete the sentence regarding the formation of the vertebrate retinotectal map. (2)

When the optic nerves have crossed at the chiasm, ………………… and …………………. then promote growth along the optic tracts.

A
  • L1CAM
  • Laminin
135
Q

Axons from the dorsal region of the retina must project to which region of the tectum? (1)

A

Ventral

136
Q

Axons from the ventral region of the retina must project to which region of the tectum? (1)

A

Dorsal

137
Q

Axons from the nasal region of the retina must project to which region of the tectum? (1)

A

posterior

138
Q

Axons from the temporal region of the retina must project to which region of the tectum? (1)

A

Anterior

139
Q

Name the ligand/receptor which facilitate pattern-matching of the retinotectal map. (1)

A

Ephrins/Ephs

140
Q

Describe how Ephrins/Ephs are able to match axons from specific regions of the retina to their correct region in the tectum. (5)

*Nasal axons go to posterior tectum
*Temporal axons go to anterior tectum

A

Ephrins act as inhibitory signals.

Gradient of Ephrins in tectum - lowest anterior and highest posterior.

Nasal axons must express low levels of Eph receptor so can travel into the regions of high Ephrin concentrations.

Temporal axons must express high levels of Eph receptor so cannot travel through higher levels of Ephrins in tectum, and stop in anterior region.

Dorsal and ventral axons must express intermediate levels of Eph receptor.

141
Q

This question refers to the development of the retinotectal map.

Temporal and nasal retinal axons were grown using a stripe assay.
A slide contained areas of anterior tectum and separate areas of posterior tectum.

Which areas would you expect the temporal fibres to grow on and which areas would you expect the nasal fibres to grow on? (2)

A

Temporal fibres would grow on anterior portions only

Nasal fibres would grown on both anterior and posterior portions

142
Q

True or false? (1)

The Ephrin/Eph method of matching retinal ganglion axons to their optic tectum target may also be used to match motor neurones to their target muscles.

A

True

143
Q

Briefly describe the steps required for NMJ synaptogenesis in the vertebrate embryo. (5)

A
  • Axonal growth cone makes contact with target muscle (via ligands/receptors/guidance molecules)
  • Postsynaptic receptors cluster at contact site
  • Growth cone differentiates into presynaptic terminal (bouton)
  • Each presynaptic terminal contains active zone which lies opposite a cluster of AChRs on postsynapse
  • Basal lamina forms in synaptic cleft
144
Q

Describe the structure of the NMJ at the end of embryogenesis.

How does this change during later stages of development? (2)

A
  • Functional NMJs with multiple synaptic contacts
  • During later stages there is synaptic refinement so that only one synapse remains
145
Q

Briefly describe the 2 different mechanisms of postsynaptic receptor clustering during embryonic synaptogenesis. (2)

A
  • Initial redistribution of existing AChRs
  • Altered expression of genes encoding AChR subunits
146
Q

Describe how the expression of genes encoding AChR subunits are altered during synaptogenesis. (2)

A
  • Upregulated near synapse
  • Downregulated away from synapses
147
Q

Describe the molecular mechanisms allowing postsynaptic receptor clustering at the NMJ. (4)

A
  • Agrin protein synthesised and transported down motor axons
  • Agrin incorporated into basal lamina between pre and post synapse
  • Agrin acts on muscle-specific tyrosine kinase called MuSK
  • MuSK affects Rapsyn protein which anchors AChR to the cytoskeleton
148
Q

Name the three main molecules involved in postsynaptic AChR clustering at the NMJ. (3)

A
  • Agrin
  • MuSK
  • Rapsyn
149
Q

What would you expect to see regarding AChR clustering at the NMJ in the presence of the following molecules? (3)

a) Agrin mutant
b) MuSk mutant
c) Rapsyn mutant

A

All would result in no/reduced receptor clustering

150
Q

Give two roles of the basal lamina in synaptogenesis. (2)

A
  • Marks site of synapse formation
  • Receptor clustering
151
Q

What would happen if you destroyed a muscle fibre and its connecting synapse, but left the basal lamina intact and added a new migrating axon? (1)

A

New axon would form a synapse at the site on the basal lamina which had previously been occupied by a synapse.

152
Q

Name an essential basal lamina molecule which may aid in marking the site of synapse formation during synaptogenesis. (1)

A

Laminin

153
Q

Describe how neural electrical activity is able to regulate postsynaptic AChR expression in the newly-functional NMJ. (2)

A

Neural activity represses gene expression in non-synaptic areas.

Following denervation gene expression in non-synaptic sites is upregulated.

154
Q

Describe the role of the postsynaptic dendrite in CNS synaptogenesis. (2)

A

Extends a filopodium to axonal growth cone,

then axon guidance molecules may prime the axon and dendrite for synapse formation.

155
Q

Out of neuroligins and neurexins, which is the ligand and which is the receptor? (2)

A

Neuroligins are ligands

Neurexins are receptors

156
Q

True or false? (1)

Neuroligins are expressed on the postsynaptic membrane and neurexins are expressed on the axonal growth cone.

A

True

157
Q

Describe the role of the neurexin/neuroligin connections in CNS synaptogenesis.

How does their function relate to their structures? (2)

A

Bind to form a bridge between pre- and post-synaptic neurones.

They are then able to organise the active zone and post-synaptic density.

  • Able to arrange intracellular structures because they are transmembrane proteins
158
Q

Complete the sentence regarding CNS synaptogenesis. (2)

Neuoligins and neurexins are able to organise axons and dendrites for synaptogenesis, however this seems to be dependent on an influx of …………………… into the ……………………….

A

Calcium ions

Presynaptic terminal

159
Q

Briefly describe the roles of cadherins and synCAM in CNS synaptogenesis. (3)

A

Once the synapse has been formed they stabilize it

by recruiting scaffolding proteins

and further developing the active zone and post-synaptic density.

160
Q

Give two general reasons why neurones need to modify the connections formed in the embryo. (2)

A
  • Too many synapses
  • Inaccurate wiring
161
Q

Describe in general terms, how the number of innervating neurones is matched to the size of the target tissue during development of the vertebrate nervous system. (2)

A
  • Neurones must be sustained by their target
  • However target is only able to sustain a minimal number of neurones
162
Q

Name the type of molecules produced by target tissues which enables a synapse to maintain its connection with the target. (1)

A

Neurotrophic factors

163
Q

Give two examples of neurotrophic factors, and state what type of neurones they act on. (4)

A

Nerve growth factor (NGF; for sensory and sympathetic neurones)

BDNF (for sensory neurones)

164
Q

What effect do neurotrophic factors released from target tissues have on the innervating neurone? (1)

A

Promotes survival

165
Q

True or false? (1)

Target tissues in the embryo require a functional synapse (electrical stimulation) in order to start producing neurotrophic factors.

A

True

166
Q

What effect would be seen if NGF was injected into a tissue containing dying cells? (1)

A

Dying cells would be rescued

167
Q

What effect would be seen if antibodies against NGF were injected into a tissue? (1)

A

Cell death would be triggered

168
Q

What effect would be seen in vitro if NGF was removed from a tissue sample? (1)

A

Cells would die

169
Q

True or false? (1)

It is thought that all cells throughout the body are programmed to survive, unless they get a signal to die.

A

False - all are programmed to die, unless they get a signal to survive

170
Q

True or false? (1)

During the modification of synaptic connections, the larger the target tissue, the more neurotrophins it can produce, so the more neurones survive and innervate it.

A

True

171
Q

True or false? (1)

Some neurotrophins can cause both cell survival and apoptosis, depending on which co-factor binds to the same receptor.

A

False - Some neurotrophins can cause both cell survival and apoptosis, depending on which receptor they bind to

172
Q

What is the main type of receptor which binds neurotrophins?

Name one other receptor which binds neurotrophins with lower affinity. (2)

A

Mainly tyrosine-kinase receptors

p75 binds with low affinity

173
Q

Name the receptor for NGF. (1)

A

TrkA

174
Q

Name the receptor for NT-3 (a neurotrophin). (1)

A

TrkC

But can also bind to TrkA and TrkB

175
Q

Name the receptor for both BDNF and NT4/5. (1)

A

TrkB

176
Q

Describe simply the potential pathway by which neurotrophic factors promote neuronal survival. (2)

A
  • Activate signalling pathway to decrease cytochrome C release from mitochondria
  • Cytochrome C usually activates caspases to trigger apoptosis

Neuroscience Y2S1 (16 decks)

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