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MTB x > week 6 part 1 > Flashcards

week 6 part 1 Flashcards

1
Q

How does an egg become a body?

A
  1. As a fertilized human egg divides, it first becomes a solid ball of cells, the morula
  2. Next, about five days after fertilization, it becomes a hollow ball, the blastocyst.
  3. The cells of the outer layer of the blastocyst eventually form part of the placenta

4Inside the ball is a small clump of cells, the inner cell mass, that will form all the tissues in the body

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2
Q

What are two main aspects of development?

A
  1. Proliferation of cells

2. Differentiation

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3
Q

What is differentiation?

A

become specialised to carry out specific functions in an adult body

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4
Q

What happens from the mass of totipotent cells?

A

generate the circulatory system, the nervous system, the muscles and the immune system

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5
Q

What does development depend on?

A

spatiotemporal expression of specific genes

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6
Q

What is expression regulated by?

A

hardwired molecular programmes together with epigenetic mechanisms

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7
Q

What contributes to neuronal differentiation?

A

Both external and internal factors

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8
Q

What do internal factors include?

A
  1. Cell surface and secreted molecules that control cellular fates
  2. Transcription factors that control gene expression
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9
Q

What do external factors include?

A
  1. Nutrients
  2. Sensory stimuli
  3. Social experience
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10
Q

What does neuronal tissue start with?

A

100 cells

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11
Q

What generates the brain?

A

The neural epithelial stem cells

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12
Q

Why does the neural epithelial tissue proliferate?

A

The neural epithelial stem cells undergo rapid division to increase in number

capable of generating a brain of the central nervous system

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13
Q

Starting from stem cells, what does the neural epithelial stem cells become

A

Restricted in their potential to generate different cell type

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14
Q

During mammalian CNS development, what does neural precursor cells arising from neural tube produce?

A

Pools of multipoptent and more restricted neural progenitor cells

which proliferate, migrate and further differentiate into neurons and glia cells

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15
Q

During embryogenesis, where is neural precursor derived from?

A

neuroectoderm

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16
Q

How is neural precursor detected?

A

During neural plate and neural tube formation

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17
Q

When happens when the embryo develops?

A

the neural stem cells can be identified in nearly all regions of the embryonic mouse, rat, and human CNS

including the septum, cortex, thalamus, ventral mesencephalon and spinal cord

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18
Q

What does neural stem cells have

A

spatial identity and differentiation potential

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19
Q

How is neural plate formed?

A

1.third week of development, the notochord appears in the mesoderm

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20
Q

What does notochord secrete?

A

growth factors which stimulate the differentiation of the overlying ectoderm into neuroectoderm

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21
Q

How is neural folds formed?

A

The lateral edge of neural plate rise

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22
Q

How is neural plate formed?

A

The neural folds move towards each other and meet in the midline, fusing

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23
Q

How is neural crest formed?

A

During fusion of the neural folds, some cells within the folds migrate to form a distinct cell population

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24
Q

What do neural crest give rise to?

A

diverse cell lineage – including melanocytes, craniofacial cartilage and bone, smooth muscle, peripheral and enteric neurons and glia

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25
Q

What is neurulation?

A

The formation of neural tube

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26
Q

where does the neural epithelial cells dividie initially?

A

Ventricular surface

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27
Q

What is the three primary brain vesicles divided into?

A
  1. Prosencephalon
  2. Mesencephalon
  3. Rhombencephalon
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28
Q

What does the forebrain give rise to?

A
  1. Telencephalon

2. Diencephalon

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29
Q

What is mesencephalon?

A

midbrain

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30
Q

What does Rhombencephalon give rise to?

A
  1. Metencephalon (pons and cerebellum)

2. Myelencephalon (medulla oblongata)

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31
Q

How does the development of the nervous system proceed?

A

in rostro-caudal specification of different areas

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32
Q

What is the development of nervous system controlled by?

A

very limited number of secretory factors e.g. FGF, retinoic acid, sonic hedgehog

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33
Q

How do you specify the different regions

A
  • There is a gradient – activate downstream signalling according to the concentration of growth factor present, the receptors, to the transcription factor present within the cell
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34
Q

What is responsible for induction of ventral fates ?

A

Sonic hedgehog

secreted by the notochord

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35
Q

how does diverse function of the CNS arise?

A

regionally distinct division of the neural tube

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36
Q

What is the 4 major steps in the establishment of subdivisions?

A
  1. Generation of progenitor cells in the neural plate and tube
  2. Generation of regional differences within the NT that correspond to major subdivisions of the CNS
  3. Specification of distinct neuronal subtypes
    • The influence of neuronal inputs
37
Q

How do progenitors differentiate into neurons and glial cells?

A
  1. proliferating
  2. undergo symmetric cell divisions
  3. produce neuroepithelial stem cells
38
Q

Differentiation of neural precursors?

A

Asymmetric cell division

39
Q

What is the generation of neurons and glial cells regulated by?

A
  1. Delta-notch signalling

2. Basic helix-loop-helix transcription factors

40
Q

What is first generated from ectoderm forming the neural plate?

A

Neuroepithelial cells

41
Q

What do neuroepithelial cells and undergo?

A
  1. neural stem cells

2. undergo a symmetric cell division to produce more neural stem cell

42
Q

What happens after neural tube is formed from the neural plate?

A

Neuroepithelial cells become radial glia by acquiring some glial features

43
Q

What is Notch known to inhibit and maintain?

A
  1. inhibit = neuronal differentiation

2. maintain = neural stem cells

44
Q

What are the 3 main stages of development of mammalian cerebral cortex?

A
  1. A pre-plate
  2. A cortical plate
  3. The mature pattern of layers
45
Q

How do neurons achieve their final position within the cortex?

A

Migrating along radial glial fibers

46
Q

What are neurons within the cortical plate?

A

organised into well-defined layers

47
Q

What do the cortex layers have?

A

different connectivity’s, they are responsible for transmitting different information

48
Q

What is the inside out layers?

A

the earliest born neurons will populate deep layers of the cortex, the later born ones migrate past them and populate the upper layers of the cortex

49
Q

When is most neurogenesis complete?

A

before birth

it is embryonic

50
Q

What happens at embryonic day 10-11, half way through gestation?

A

There is a huge expansion of neuroepithelial stem cells in the cortex

51
Q

What is the neuro epithelial cortex?

A

single cell layer pseudo-stratified epithelium

52
Q

What gives cortex an appearance of being multi-layered?

A

During the cell cycle, the cell body of the neuroepithelial cells migrate up and down

53
Q

When does neurogenesis in the cortex in neuron cortex start?

A

embryonic day 13 and proceeds at about day 17 which is near birth

54
Q

What is the ventricular zone?

A

a degree is a stem cell niche – when the cells lose their contact with the stem cell niche, they begin to commit to differentiating and becoming post-mitotic neurons

55
Q

What does the intermediate progenitor undergo?

A

divisions and will form the sub-ventricular zone – another proliferative layer

56
Q

What does different transcription factors specify?

A

neurons present in different layers

57
Q

What do Radial glial cells serve?

A

neural progenitors and structurral scaffold

58
Q

What is only expressed when radial glial become neurons?

A

RNA-binding protein called HU

59
Q

How do you study the behaviour of neural stem cells?

A

plating them in culture, isolate the cortices at different stages of embryonic development – dissociate them and plate the cells

60
Q

When does neurogenesis really begin?

A

Embyronic day 13

61
Q

What is Oligodendrocytes marked by?

A

Expression of O4+

62
Q

What are all cells of CNS generated from?

A

Neural stem cell (NSCs)

The tissue stem cells which give rise to all neural lineage cells

63
Q

What are NSC specified in?

A
  1. Space

2. Time

64
Q

What do NSC depend on?

A

selective activation or silencing of lineage-specific genes by lineage-specific transcription factors (bHLH)

65
Q

What does Transcription factors ensure?

A

Appropriate chromatin remodellers are recruited to specific gene regulatory elements

66
Q

What are neurotrophins?

A

secreted growth factors which are absolutely essential for the survival of neurons

67
Q

What is P75?

A
  1. P75 neurotrophin receptor (low affinity receptor)

2. doesn’t have any enzymatic activity but share homology with the TNF

68
Q

What is TRK receptors?

A

tryosine kinases

initiate cascade of events

69
Q

What shows a clear preference for the different neurotrophin?

A

• TrkA, TrkB, TrkC

70
Q

What does TrkA bind to?

A

preferentially to NGF with high affinity

71
Q

What does TrkB bind to?

A

BDNF and NT4/5 and TrkC is receptor for NT-3

72
Q

Where was SC1 cloned from?

A

schwann cell library and it binds to the cytosolic domain of the P75

73
Q

What are proteins that contain subdomains?

A
  1. Histones
  2. Lysines
  3. Methyltransferases
74
Q

What are PRDM proteins involved in?

A

Epigenetic control of gene expression during development

75
Q

What does TUJ1 express?

A

post mitotic neurons

76
Q

What is controlled by levels of PRDM4?

A

The timing of the differentiation

77
Q

What can protein Arginine Methyltransferases (PRMTs) promote?

A

non-methylation of arginine on nitrogen atom

78
Q

What does type 1 and type 2 of PRMTs mediate?

A
  1. Type 1 =mediate asymmetric di-methylation nitrogen

2. Type 2 =mediate symmetric di-methylation

79
Q

What are the two enzymes that mediate this reaction?

A
  1. PRMT5

2. PRMT9

80
Q

What is positive for neural stem cell?

A

Nestin

81
Q

Where do you delete SC1?

A

dorsal cortical precursors

82
Q

Where is FMRP implicated in?

A

Fragile X syndrome

83
Q

What do Hu proteins do?

A

Trigger development of autoimmune neurological diseases

84
Q

Where is FUS implicated in?

A

FTD/ALS

85
Q

Where is SMN implicated in?

A

in spinal muscular atrophy

86
Q

What are the major challenges in regeneration within CNS?

A
  1. neurons are post-mitotic
  2. A huge variety of neurons within the brain
  3. Connectivity which is essential for proper neuronal function
87
Q

What are a huge variety of neurons within the brain?

A
  • They are functionally different
88
Q

What displays discrete brain regions?

A

Organisation of the cerebral organoids

MTB x (15 decks)

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