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3rd Year Biomed > Neuroscience Lecture 1-2 - Formatting and patterning of the nervous system > Flashcards

Neuroscience Lecture 1-2 - Formatting and patterning of the nervous system Flashcards

1
Q

Explain simply the first 6 stages of mammalian embryo cleavage

A

1) 2 cell (30-36hr)
2) 4 cell (40hr)
3) Early 8 cell (50-60hr)
4) Compacted 8 cell stage
5) Morula - 16 cell (3-4 days)
6) Blastocyst (4-5 days)

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2
Q

What is the name of cells in embryo cleavage?

A

Blastomere

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3
Q

What occurs to produce the compacted 8 cell stage?

A

Blastomeres adhere using tight and gap junctions

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4
Q

What does the morula consist of?

A

Inner cell mass (totipotent cells which produce the foetus) and the trophoblast cells (form the chorion)

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5
Q

What occurs in cavitation?

A

Trophoblast cells secret fluid into morula to create cavity called the blastocoel

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6
Q

What is the path of the blastocyst?

A

Grows to 64 cell stage as it moves through the oviduct
- in the uterus, implants into uterine wall using adhesion molecules and proteases that digest extracellular matrix of wall

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7
Q

What 2 distinct layers form from the inner cell mass of the blastocyst?

A

Epiblast and Hypoblast

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8
Q

What 3 things does the epiblast give rise to?

A

The 3 germ layer:
Ectoderm
Mesoderm
Endoderm

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9
Q

What is gastrulation?

A

Phase in early embryonic developement when the bilaminar germ disc (epiblast and hypoblast) is converted into a trilaminar structure (ectoderm, mesoderm and endoderm)

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10
Q

What occurs in gastrulation?

A

1) Appearance of the primitive streak (thickened epilast)
2) Streak extends from posterior to anterior due to intercalation of surrounding cells (convergent extention)
3) A groove (primitive groove) forms within streak allowing cell migration into deeper layers
4) Formation of Hensens node - thickening of anterior end of streak with a pit at the centre
5) Epiblast cells migrate inwards through the pit

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11
Q

What occurs to the epiblast cells that migrate through the primitive pit?

A

1) Some cells move ventrally, displace the hypoblast cells and form endoderm
2) Some sit between the forming endoderm and epiblast cells and become the mesoderm
3) Epiblast cells that do not migrate become ectoderm

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12
Q

What 3 structures do the ectoderm form? Give an example of some things that these structures then go on to form

A

Ectoderm forms:

  • Surface ectoderm
  • Neural plate
  • Neural crest

Surface ectoderm:
Skin, hair, nails, lens and cornea of eye

Neural plate:
Brain, spinal cord, retina

Neural crest:
PNS, adrenal medulla

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13
Q

Give some examples of structures the mesoderm becomes

A

Cartilage, bone, muscle, blood, lymph vessels, kidney, spleen

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14
Q

Give some examples of structures the endoderm becomes

A

Epithelial lining of digestive tract, respiratory tract, bladder, urethra

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15
Q

What main signalling pathway influences neural development?

A

One tissue influences the fate of another through inductive interactions
- Signalling molecules from one tissue act on receptors of another nearby tissue

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16
Q

What is the default pathway of the ectoderm? Neural fate or epidermal fate?

A

Neural fate

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17
Q

What signalling molecule is required in order to induce epidermal fate of the ectoderm?

A

Bone morphogenetic protein (BMP)

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18
Q

How is BMP prevented from signalling ectoderm cells so that they remain of neural fate?

A 
Organiser tissue (Hensons node) secretes BMP inhibitors:
- Noggin
- Follistatin
- Nodal related 3
that stabalise neural fate
Organiser precursors produce:
- Wnt
- Fibroblast growth factor (FGF)
inhibit BMP signalling
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19
Q

What mesoderm component induces neural plate formation?

A

Notochord (differentiated mesoderm cells)

20
Q

What is neurulation?

A

Process by which the neural plate forms the neural tube that becomes the CNS

21
Q

What cells form the neural plate?

A

Dorsal ectoderm cells

22
Q

What are the 5 stages of primary neurulation?

A

1) Formation
- Cells of dorsal ectoderm elongate - groove forms at midline
2) Folding
- Hinge point forms, midline of plate anchored to notochord
3) Elevation
Folds of plate elevate
4) Convergence
- Hinge points form at neural plate-neural crest border
- Folds of plate converge towards te midline
5) Closure
- Folds meet and adhere at midline
3 distinct layers:
- Top - epidermis
- Neural crest cells
- Bottom - neural tube

23
Q

What are the 3 initiation sites of neural tube closure in mice?

A

1) Future hindbrain-cervical spine boundary
2) future forebrain-midbrain boundary
3) rostral extremity of the future forebrain

24
Q

What are the 4 neural tube defects and what causes each?

A

1) Anencephaly - failure to close the anterior neural tube (closure 2)
2) Craniorachischisis - failure of closure 1
3) Open spina bifida - failure to close posterior neural tube
4) Spinal dysraphism - secondary neurulation defect at very base of spinal cord

25
Q

What are the main 3 causes of neural tube defects?

A

1) Folic acid deficiency
2) Environmental factors
- Crop contaminant fumonisin
- Anti-convulsant valproic acid
3) Genetic predisposition
Genes involved in:
- Folate metabolism
- Neural tube closure eg Wnt, its receptors and pathway molecules

26
Q

What signalling pathway is required for convergent extension occur?

A

Non-canonical Wnt signalling via the planar cell polarity (PCP) pathway

  • Causes remodelling of the actin cytoskeleton
27
Q

This card should be earlier on, to do with the neural plate
The gradient of what component determines the anterior-posterior axis of the neural plate?

A

Gradient of Wnt

  • Wnt high at posterior end
  • Wnt inhibitors produced at anterior end
28
Q

This card should be earlier on, to do with the neural plate
The gradient of what component determines the mediolateral axis of the neural plate?

A

BMP

  • BMP signalling high laterally and declines towards the midline
  • BMP inhibitors produced by axial mesendoderm (AME)
29
Q

Describe the regionalisation of the neural tube in the 3-vesicle stage?

A

Vesicle 1 - top
- Prosencephalon (forebrain)

Vescile 2 - down from 1
- Mesencephalon (midbrain)

Vesicle 3 - Rhombencephalon (hindbrian)

Then, the caudal neural tube - will become the spinal cord

30
Q

Give some examples of what the prosencephalon will beome?

A
  • Cerebral cortex
  • Basal ganglia
  • Limbic system
  • Thalamus
  • Hypothalamus
  • Pineal gland
31
Q

Give some examples of what the Mesencephalon will become

A
  • Colliculi
  • Substantia nigra
  • Red nuclei
32
Q

Give some examples of what the Rhombencephalon will become

A
  • Cerebellum
  • Pons
  • Medulla
33
Q

What are neuromeres?

A

Segment like swellings that act as development compartments in the neural tube

34
Q

What are neuromeres called in the hindbrain?

A

Rhombomeres

35
Q

What establishes the rhombomere compartments?

A

Adhesion between cells

36
Q

What establishes rhombomere boundaries?

A

Ephrin-Eph receptor signalling

  • Ephrin ligand only present in even numbered rhombomeres
  • Eph receptors only found in odd
37
Q

What are homebox genes?

A
  • Genes that encode DNA binding transcription factors that regulate gene expression
38
Q

What are the characteristics of homeobox genes and what is the stucture of their gene products?

A
  • 180 nucleotide sequence (homoebox)
  • Code for 60 AA sequence (homeodomain)
  • Have 3 alpha helices
  • Helix 3 recognises major groove of DNA
39
Q

What are the names of some homeobox genes?

A
  • Hox
  • Orthodenticle (Otx)
  • Gastrulation brain homeobox (Gbx)
  • Engrailed (En)
  • LIM
40
Q

What is the distribution of Otx and Gbx in the neural tube? What chemical gradient do they use to form that way?

A
  • Future forebrain and midbrain cells express Otx
  • Hindbrain expresses Gbx
  • In response to Wnt gradient
41
Q

Where is engrailed positioned and what is its job?

A
  • Positioned at the midbrain-hindbrain border

- Acts as the organising centre (isthmic organiser)

42
Q

How do engrailed, Otx and Gbx direct anterior-posterior pattering of the neural tube?

A
  • Engrailed secretes fibroblast growth factor (FGF8)
  • FGF8 diffuses to midbrain and hindbrain
  • In presence of Otx in the midbrain, dopaminergic neurons form
  • In the presence of Gbx in the hindbrain, serotonergic neurons form
43
Q

Describe the distribution of Hox genes in the hindbrain and spinal cord

A
  • Each hindbrain rhombomere and each region of the spinal cord expresses a different set of Hox genes
44
Q

How is Hox expression maintained and what does it cause?

A
  • Mutual repression between Hox genes establishes and maintains expression patterns
  • Hox expression pattern determines type of neuron than develops in region
45
Q

Where to sensory neurons, somatic motor neurons and autonomic neurons enter or leave?

A

Sensory:
Cell bodies in the dorsal root ganglion
Enter the dorsal side

Somatic motor:
Cell bodies in the ventral horn of spinal cord
Leave the cord in ventral root

Autonomic:
Positioned in between

46
Q

How do Sonic Hedgehog (sHg) and BMP proteins determine dorso-ventral patterning of the neural tube?

A

1) Sonic Hedgehog
- sHg expressed in notochord
- sHg expression induced in floor plate (ventral (bottom) side of the neural tube)
- V-D gradient of sHg
- Concentration of sHg determines ventral neurons

2) BMP
- Expressed in epidermis
- Induced expression in roof plate (dorsal side (top))
- D-V gradient of BMP
- Concentration of BMP determines dorsal neurons

47
Q

How does the sHg gradient cause ventral patterning?

A
  • sHg binds to Patched-Smoothened receptor
  • Activates intracellular sigalling resulting in Gli zinc finger transcription factor activation
  • Gli transcription factors repressed in absense of sHg
  • Therefore, ratio of activator and repressor Gli proteins creates a Gli gradient
  • Gradient regulates expression of homedomain transcription factors

3rd Year Biomed (44 decks)

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