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BMS 249 - Developmental Neurobiology > Neural migration in CNS development > Flashcards

Neural migration in CNS development Flashcards

1
Q

Where are neurons born?

A

In the ventricular zone

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2
Q

Which 2 ways do neurons migrate?

A

1) Radially from the ventricular zone

2) Migrate tangentially

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3
Q

What do tangential migrations allow neurons to do?

A

Mix neurons up

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4
Q

How do cells initially divide at the ventricular zone?

Later on, how do cells divide?

A
  • Symmetrically, giving rise to 2 daughter cells which are identical to the mother cell
  • Asymmetrically, giving rise to a radial glia cell and neural precursors
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5
Q

How do the mature neurons accumulate in the mantle zone over time?

A

Neural precursors migrate outwards along the process of the radial glia

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6
Q

What is birth-dating and what did this show?

A
  • Inject tritiated thymidine into pregnant females - incorporated into newly synthesised DNA at S phase
  • When the cells divide, the tritiated thymidine is diluted out (cells with a more dilute TT are older)
  • Can follow where cells are born and can trace what happens to theses cells overtime
    (can trace their migration to their final destination overtime)
  • Showed that neurons born at different times migrate to different layers of the cortex, from the VZ to the MZ
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7
Q

What is more widely used to birth-date cells, other than tritiated thymidine?

A

BrdU

Bromodeoxyuridne

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8
Q

What is each layer of the cortex characterised by?

What does this indicate?

A

Different neurons which are expressing a different set of transcription factors

Indicates that neurons born at different times have different fates

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9
Q

How does the cortex develop from the migrating layers of the cortex?

A

Inside-out:

So that the neurons born first occupy the deepest layer and the neurons born last occupy the highest layer

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10
Q

How many layers of the cortex are there?

A

6

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11
Q

What must happen to the radial glial cells to produce neuronal precursors with different fates?

A

They must undergo changes

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12
Q

What do herrochronic transplant show about the fates of the neuronal precursors?

How was this shown?

A

Precursors have the ability to adopt many fates, but this is lost in older precursors

  • Earlier precursors were transplanted in to an older host at the VZ - migrated to adopt the cells born at the same time in the host (their fate is plastic)
  • Late born precursors, when transplanted into a younger host, migrated and adopted the fate of the position they would have done if weren’t transplanted
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13
Q

What is Lissencephaly what does it cause?

A

A brain which is agyria (sulci and gyri are deminished or absent)

Failure or abnormal neuronal migration

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14
Q

In Lissencephaly, where are most of the neurons found and why?

A

In the deeper layers

Mutations in the genes associated with microtubule function, meaning that the neuronal precursors cannot migrate up the radial glial cell

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15
Q

What causes Lissencephaly?

A

Mutations in the genes of proteins associated with microtubule function

  • Alpha tubulin (TUBA1A)
  • Beta-tubulin (TUBB2B)
  • Microtubule associate proteins (LIS1, DCX)
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16
Q

Why are mutations in proteins associated with microtubule function detrimental?

A

Microtubules are critical for the migration of the neuronal precursors up the radial glia

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17
Q

Before the 6 layers of the cortex can form, what must happen?

A

2 layers must form the PREPLATE

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18
Q

Which cells form the preplate and where are they located?

A 
Cajal Retzius cells (in the marginal zone)
Subpplate neurons (below)
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19
Q

What is the cortical plate and where does it form?

A

Made of the 6 layers of the cortex

Lies between the cajal retzius cells at the marginal zone, and the subplate

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20
Q

Once the cortical plate has formed, what happens to the subplate neurons?

A

They die

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21
Q

What is the role of the subplate neurons?

A

To guide incoming thalamic axons

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22
Q

When were cajal retzius cells discovered?

A

In 1890

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23
Q

Which are the first post-mitotic cells to appear in the brain?

A

Cajal Retzius cells

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24
Q

What happens to Cajal Retzius cells post natally?

A

They change shape and die

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25
Q

How was is discovered that CR cells tell migrating cells when to stop? (in mice)

A

Studies of a reeler mouse:
- Mutation in reelin gene encoding a large ECM protein expressed specifically by CR cells

  • Caused the failure of CR cells and subplate cells to separate
  • Therefore disruption of the layering of the cortex
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26
Q

What do Cajal Retzius cells do?

A

Stop newly born cortical plate cells from migrating anc cause them to differentiate

27
Q

In humans, what do reelin mutations cause?

A

Lissencephaly

28
Q

What happens to the radial glia cell progenitor pool at the ventricular zone over time?

A

It becomes depleted as the cells divide symmetrically to give 2 neuronal precursors

29
Q

What happens to a subset of radial glia cells at the VZ as the radial glial progenitor pool becomes depleted and why?

A

They become astrocyte-like and remain at the VZ as adult stem cells

30
Q

What are the 2 major zones of adult stem cells?

A

Sub ventricular zone of the 4th ventricle

Dentate gyrus of the hippocampus

31
Q

Where do the inhibitory interneurons of the cortex migrate in from and how do they migrate?

A

The subpallium

Migrate tangenitally over large distances as neuronal precursors

32
Q

Which neurons are not generated in the cortex?

A

Inhibitory interneurons

33
Q

Where do different types of inhibitory interneuron precursors migrate to?

A

Olfactory bulb (dopaminergic inhibitory interneurons)

Striatum (Cholinergic inhibitory interneurons)

34
Q

What 3 methods can be used to trace neuronal migration?

A

1) Injection of lipophilic dyes (birth-dating)
2) Transplantation experiments
3) Virus injection

35
Q

How does injecting a virus allow to trace neuronal migration?

A

They infect the VZ and may carry a GFP - can trace the cells which have become infected

36
Q

Where is the cerebellum located?

A

Over the 4th ventricle, above the medulla

37
Q

What is the cerebellum important in?

A

Motor learning

38
Q

What is the structure of the cerebellum?

A

Highly folded

Has a cortical region (made of many layers) and a central nuclei

39
Q

Where does the cerebellum arise from and in what shape?

A

As a open structure rhombus shaped, from the specialised roof-plate cells at the boundary of the mid and hind-brain

40
Q

What are rhombic lip cells?

A

Highly proliferative roof-plate cells at the midbrain-hindbrain interface

Formed by the joining of the roof plate

41
Q

What do the daughters of the rhombic lip cells do?

A

Migrate, but stay in the hindbrain and become the neurons of the cerebellum

Proliferate as they move over the surface of the anterior medulla

42
Q

What do the cells of the anterior rhombic lip become?

A

Granule neuron precursors

43
Q

What do the cells of the posterior rhombic lip become?

A

Pontine nuclei and inferior olive

44
Q

What happens during development of the cerebellum?

A
  • EGL cells proliferate and at the same time, cells start to differentiate
  • At the same time as differentiating, they migrate tangentially, extending their axons
  • Eventually (once differentiated) their cell body ‘absails’ into the IGL past the PCL and into the IGL
  • Leaving their axons behind
45
Q

After the EGL cell bodies have migrated into the IGL, what happens to the axons they have left behind?

A

They make synapses with purkinje cell dendrites

46
Q

Where are granule cells born?

A

At the OUTSIDE of the cerebellum

47
Q

Where are purkinje cells born?

A

At the ventricular zone

48
Q

What regulates rhombic lip cell production?

A

MATH-1 transcription factor

49
Q

What happens if MATH-1 is inhibited?

A
  • No layering
  • No IGL
  • No pontine nuclei
50
Q

What stimulates mitosis (cell proliferation) in the EGL?

A

Shh release from the Purkinje cells

51
Q

In Reeler mice, what happens in the cerebellum?

A

Disordered layers

52
Q

What does the level of Shh effect?

A

The amount of lobulation in the brain, which differes between species

53
Q

What do mutations in Shh cause?

A

Medulloblastoma (bulging of the brain in children - tumor)

54
Q

How can tridiated thymidine be seen in the cells and why?

A

Using an antibody - tridiated thymidine has an epitope

55
Q

Using tridiated thymidine, how was it possible to see the neurons born at different times migrated to different layers of the cortex?

A

Inject into mice at different stages of pregnancy

56
Q

What do subplate neurons play an important role in?

A

Guiding thalamic neurons

57
Q

Along with inhibitory interneurons for the cortex, what other neurons migrate from the subpallium? (3)

A

1) GABA-ergic interneurons
2) Dopaminergic inhibitory interneurons
3) Cholinergic inhibitory interneurons

58
Q

In the cerebellum, where do the cell bodies of the granular cells lie?

A

In the inner granular layer

59
Q

In the cerebellum, where do the axons of the granular cells lie?

What do they synapse with?

A

In the molecular layer, above the purkinje cells

Synapse with the purkinje cell dendrites

60
Q

In the cerebellum, what are the main output neurons?

A

The purkinje

61
Q

What is the developing cerebellum continuous with and what does this form?

A

The roof plate of the lower spinal cord, forming a rhombic lip (as the developing cerebellum is an open structure- roof plate slightly hangs over)

62
Q

How do anterior rhombic lip cells migrate?

A

Initially anteriorwards and then tangenitally

63
Q

Why in mice with a reeler mutation, do the mice become ataxic?

A

Due to disordered layers in the cerebellum, which is involved in motor learning

64
Q

What is ataxia?

A

Lack of voluntary coordination of muscle movements

BMS 249 - Developmental Neurobiology (16 decks)

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