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3rd Year Biomed > Neuroscience lectures 3-4 - Neurogenesis > Flashcards

Neuroscience lectures 3-4 - Neurogenesis Flashcards

1
Q

What are the 3 zones of the neural tube?

A

1) Ventricular zone
2) Intermediate zone
3) Marginal zone

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2
Q

What does the ventricular zone contain?

A

Multipotent stem cells

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3
Q

What do the multipotent stem cells in the ventricular zone give rise to?

A

Neurons and glia

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4
Q

How do the cells of the neural tube divide?

A

Mitosis

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5
Q

What occurs to cells produced from the multipotent stem cells?

A

They migrate away to create additional layers - earliest born remain closest to ventricular zone

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6
Q

What are the layers of the cerebellum, from ventricular zone outwards?

A

1) Ventricular zone
- Intermediate
- Internal granule layer
- Purkinje cell layer
- Marginal zone
- External granule layer

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7
Q

What are the layers of the cerebral cortex from ventricular zone outwards?

A
  • Ventricular zone
  • sub-ventricular zone
  • indermediate zone
  • cortical plate
  • marginal zone
  • molecular layer
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8
Q

What are the 2 main modes of cell division in the neural tube?

A

1) Symmetric

2) Asymmetric

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9
Q

What is the purpose of symmetric cell division of stem cells?

A
  • Self renewal/expansion of stem cell population
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10
Q

What are the 2 types of asymmetric stem cell division?

A

a) Stem cell divides to produce a neuron and another stem cell
b) A neuron and a glial cell

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11
Q

When does neurogenesis start?

A

Begins during the first few weeks of embryogenesis and continues rapidly after birth?

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12
Q

When does neurogenesis begin to slow?

A

At around age 1 and a half

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13
Q

How many neurons are added per minute and how many synapses per second during early postnatal development?

A
  • approc 250,000 neurons per minute

- 30,000 synapses/cm^2 of cortex formed per second

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14
Q

How long does neurogenesis continue until?

A

Early 20’s

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15
Q

Where are adult neural stem cells (NSCs) found?

A

In the hippocampus

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16
Q

What are adult NSCs involved in?

A
  • Learning and memory

- In the olfactory bulb

17
Q

In animal models, what is the effect of both an active, interesting environment vs a stressful environment on adult hippocampal neurogenesis?

A
  • Adult hippocampal neurogenesis increases in interesting environment
  • Decreases in stressful environment
18
Q

What could adult NSCs potential be used to treat?

A

Brain injury or/and neurodegenerative diseases

19
Q

What is the challenge in using adult NSCs as therapeutics?

A

To trigger the cells to differentiate into specific neuronal types

20
Q

What 2 groups of genes are involved in cell signalling to decide neuronal cell fate?

A

1) Proneural genes

2) Neurogenic genes

21
Q

What do proneural genes encode?

A

Basic helix-loop-helic (bHLH) transcription factors e.g Achaete-scute complex, AS-C

22
Q

What do the neurogenic genes encode?

A

1) Surfave ligand-receptor pair
- Delta (ligand)
- Notch (receptor)

2) Downstream bHLH transcription factors
e. g C-promoter binding factor CBF-1 and Hairy and E(spl) (HES)

23
Q

Explain the process of lateral inhibition (delta-notch signalling) in determining cell fate

A

1) Cell 1 and 2 express same level of notch and delta (equivalent)
2) Cell 1 expresses more delta, increasing notch activation in cell 2 (equivalence lost)
3) In cell 2, cleavage of notch yields Notch-intra which activates bHLH cascade in nucleus - represses achaete-scute
4) Reduction in achaete-scute lowers Delta levels in Cell 2 reducing Notch activation in Cell 1
5) Lower Notch in cell 1 allows achaete-scute levels to rise, increasing Delta expression in cell 1 and notch activation in cell 2

LOW Notch HIGH delta cells (cell 1) are neuronal precursors

HIGH Notch LOW Delta cells (Cell 2) are non-neuronal cells - can become glia

24
Q

Name the 3 ways the neurons can migrate in the developing embryonic cortex?

A

1) Migration along radial glial cells (radial migration)
2) Migration along axon tracts (Tangential migration)
3) Migration without a scaffold (Free migration)

25
Q

When are radial glial cells produced and where do they span from and to?

A
  • Arise early in neurogenesis
  • Cell body in the ventricular zone (inner surface)
  • Process extends from inner to outer surface and is fixed at each end
  • Acts as a track for migrating neurons to move along choo choo
26
Q

What is nucleokinesis?

A

Extension of the leading process and movement of the cell body and nucleus into it

27
Q

Describe nucleokinesis in radial migration

A
  • Neuron extends a leading process in the direction of migration
  • Centrosome localises to migrating side of nucleus and extends microtubules (MTs) into the leading process
  • MTs form a cage like structure around the nucleus
  • Nucleus translocates into the leading process
  • The trailing edge retracts

Summary:

1) Leading process moves forward
2) Nucleus moves to leading process
3) Retraction of trailing edge

28
Q

What molecules are are associated with the MTs?

A

1) Dynein motor and associated proteins Ndel1 and Lis1

2) Doublecortin (Dcx) which stabilises MTs

29
Q

How does the nucleus move into the leading process?

A

With the aid of the dynein-Lis1-Ndel1 complex

30
Q

What is Lissencephaly?

A

A group of disorders arising from cortical or general brain malformation

31
Q

Name 2 disorders that arise from Lis1 mutations

A
  • Type 1 lissencephaly

- Isolated lissencephaly sequence (ILS)

32
Q

Name a disorder that arises from a doublecortin mutation

A

X linked ILS

33
Q

Name a disorder that arises from a Reelin mutation

A

Autosomal recessive lissencephaly with Cerebellar Hypoplasia (LCH)

34
Q

Name a disorder that arises from Ndel1 mutations

A

Microlissencephaly - extreme microcephaly with lissencephaly

35
Q

What are cortical gyri and sulci and when do they form?

A

Different parts of a cortical fold
Gyri = top of fold/ridge
Sulci = the groove/depression

  • Form as more neurons are produced
36
Q

What is the appearance of a type 1 lissencephaly brain compared to a normal brain?

A
  • Reduced gyri (fewer folds - smoother)
  • Abnormal cortical layers
  • Enlarged ventricles
37
Q

What is the appearance of a microlissencephaly brain?

A
  • Drastic reduction in size
  • Absense of corpus callosum
  • Limited motor and cognitive development

3rd Year Biomed (44 decks)

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