Development of the Nervous System Flashcards
1
Q
What are the main steps in the development of the nervous system?
A
Neural induction Neurulation Morphogenesis and patterning of neural tube Neurogenesis Neuronal migration Axon growth and pathfinding, and dendritic arborisation Synaptogenesis Gliogenesis/myelination
2
Q
Define neural induction
A
Assigning neural potential to region of early embryo
3
Q
Define neurulation
A
Forming rudimentary nervous system
4
Q
Define neurogenesis
A
Production of neurons and glia from precursor cells
5
Q
Define neuronal migration
A
Neurons move from sites of production to positions in mature brain
Makes space for new neurons
6
Q
Define synaptogenesis
A
Making and refining synaptic connections
7
Q
In what stages of nervous system development does apoptosis occur?
A
Neurogenesis Neuronal migration Axon growth and pathfinding, and dendritic arborisation Synaptogenesis Gliogenesis/myelination
8
Q
Which part of the embryo acquires a neural fate?
A
Region of dorsal embryonic ectoderm = neural plate
9
Q
What forms from the neural plate?
A
Entire CNS
10
Q
What happens to the rest of the ectoderm?
A
Acquires epidermal fate
11
Q
What determines epidermal fate?
A
Local bone morphogenetic protein (BMP) signalling
12
Q
What is the organiser region of the neural plate, and what does it do?
A
Intermediate marginal zone
Cells underneath programmed to secrete inhibitors that stop cells above from becoming epidermis - block BMP signal
13
Q
What is a neurula?
A
An embryo that has undergone neural induction
Happens at 3 weeks
14
Q
What is neurulation?
A
Formation of the neural tube
15
Q
How is the neural tube formed?
A
Neural plate cells become more columnar Elevation of neural folds Neural folds fuse in dorsal midline Neural tube pinches off from epidermis Occurs all the way along the embryo
16
Q
What is the inside of the neural tube, and what does it contain?
A
Ventricle
Contains fluid
17
Q
In which direction does the neural tube zip up?
A
Bidirectionally from initial point of closure
18
Q
Where are the two points of closure of the neural tube?
A
Hindbrain-cervical boundary
Forebrain-midbrain boundary
19
Q
What causes neural tube defects?
A
Failure of neural fold formation or closure
20
Q
What doesn’t close in spina bifida?
A
Caudal neuropore
21
Q
What doesn’t close in anencephaly?
A
Cranial neuropore
22
Q
What is the role of folate thought to be?
A
Enhancing cellular competency
23
Q
Where do neural crest cells develop?
A
At neural plate margin
24
Q
When do neural crest cells migrate?
A
When dorsal margins of tube fuse
25
Where do neural crest cells migrate?
From dorsal to ventral side
26
What do neural crest cells give rise to?
```
Dorsal root ganglia
Sympathetic ganglia
Adrenal medulla
Enteric NS ganglia
Melanocytes
Schwann cells
Cartilage and bone of face and jaw
```
27
What happens after the neural tube closes?
Primary and secondary brain vesicles form
28
Describe the primary and secondary brain vesicles
Wall = neuroepithelium
| Fluid-filled central cavity = ventricular system
29
What are the three vesicles that form at the rostral end of the neural tube?
```
Prosencephalon = forebrain
Mesencephalon = midbrain
Rhombencephalon = hindbrain
```
30
What does the prosencephalon split into?
Telencephalon
| Diencephalon
31
What does the rhombencephalon split into?
Metencephalon
| Myelencephalon
32
What does the telencephalon give rise to?
Olfactory bulb
Cerebral cortex
Hippocampus
Striatum/basal ganglia
33
What does the optic vesicle give rise to?
Retina
34
What does the diencephalon give rise to?
Thalamus
| Hypothalamus
35
What does the mesencephalon give rise to?
Midbrain
36
What does the metencephalon give rise to?
Pons
| Cerebellum
37
What does the myelencephalon give rise to?
Medulla
38
What provides the different positional cues for specifying cell fate?
Gradients of morphogens from patterning centres or organising regions
39
What induces the roof plate?
Overlying ectoderm
40
What does the roof plate secrete?
Dorsalising morphogens
41
What induces the floor plate?
Underlying notochord
42
What does the floor plate secrete?
Ventralising morphogen
43
What cell types are derived because of the roof plate?
Interneurons
| Oligodendrocytes
44
What cell types are derived because of the floor plate?
Motor neurons
45
How many layers does the neuroepithelial lining of the brain vesicles have?
1
46
Why do the neuroepithelial cells in the vesicles appear multi-layered?
Nucleus develops at ventral end
Cell extends processes dorsally
Nucleus moves up and down processes with different phases of cell cycle
Called interkinetic nuclear migration
47
Where are neuroepithelial cells and what do they give rise to?
In ventricular zone
Self-replicate
Give rise to radial glia
48
Where are radial glia and what do they give rise to?
In ventricular zone
| Self-replicate, and give rise to intermediate progenitors and astrocytes = asymmetrical cell divisions
49
Where are the intermediate progenitors and what do they give rise to
In sub-ventricular zone
| Give rise to neurons
50
What are radial glial cells?
Neural stem cells
51
What are symmetric divisions?
Produce two identical daughter cells
Expand neuroepithelial progenitor pool early
Give rise to two neurons late
52
What are asymmetric divisions?
Produce two different daughter cells
| Radial glia divide and produce a radial glial cell and a differentiated neuron
53
What is the structural role of radial glia?
Provide scaffold for radial migration of neuron progeny
54
Where do the neuronal progeny of radial glia migrate to?
Away from ventricular zone towards pial surface of brain
55
What is the order of cortical layer formation?
Earliest form preplate
Preplate splits into marginal zone and subplate when first wave of cortical plate neurons arrive
Neurons of cortical plate assemble into layers II-VI in inside-out way
- Deepest layers first
56
Where are the stem cells of the adult brain?
At ventricle
57
What do stem cells of the adult brain produce?
Neurons for olfactory bulb
58
Where are cortical interneurons produced?
Basal forebrain
59
Along what do olfactory bulb neuroblasts migrate?
Rostral migratory stream
60
Where do cerebellar granule cell precursors originate>
Rhombic lip
61
What are some neuronal migration disorders?
```
Schizencephaly = clefts in brain
Lissencephaly = smooth brain
Agyria = lack of folds
pachygyria = thick folds
Polymicrogyria/microgyria = many/small folds
Neuronal heterotopia = other place, including band heterotopia = double cortex
Agenesis of corpus callosum
Agenesis of cranial nerves
```
62
What are some symptoms of neuronal migration disorders?
Vary
Poor muscle tone and motor function
Seizures
Developmental delay and impaired cognitive development
Failure to grow and thrive, and difficulties with feeding
Smaller than normal head
63
How is grey matter heterotopia formed?
Neurons fail to migrate from ventricle, or migrate halfway to cortical plate
64
What is the result of grey matter heterotopia?
Disorganised patches or bands of misplaced neurons
65
What is band heterotopia caused by?
DCX mutation on X chromosome
66
What happens in band heterotopia?
Neurons that fail to migrate accumulate below layer of white matter
67
How does a cobblestone cortex occur?
Neurons overshoot cortical plate and reside in layer I
68
Are neurogenesis and gliogenesis controlled by the same transcriptional programs?
No
| They also inhibit each other
69
What occurs first: neurogenesis or gliogenesis?
Neurogenesis
70
What proportion of neurons are pyramidal?
80%
71
What do pyramidal neurons do?
Excitatory long-range projection neurons
| Axons project to other cortical hemisphere or sub-cortical targets like spinal cord
72
What proportion of neurons are interneurons?
20%
73
What do interneurons do?
Mainly locally-projecting inhibitory neurons
| Modulate cortical excitatory output
74
How does the dendritic arbor develop?
```
Basic plan genetically specified
Growth and branching influenced by environmental factors
- Local signals
- Contact-dependent
- Diffusible cues
- Active synapses
```
75
How do dendrites and axons grow?
Repulsion of outgrowing axon
Attraction of apical dendrite
Elongation/retraction and branching of apical/basal dendrites
Activity-dependent spine stabilisation
76
What controls the extent of the dendritic arbor?
Growth factors
77
Where does axon growth happen?
At the very motile tip of the neurite = growth cone
78
What do actin filaments do in growth cones?
Regulate shape and directed growth of growth cone
79
Where are these actin filaments in the growth cone?
Filopodia
80
What do microtubules do in the growth cone?
Provide structural support to axon shaft
Essential for axon extension
Help push growth cone forward
81
When do microtubules grow in?
After actin filaments stabilise
82
What sort of environmental guidance cues steer growth cones?
Gradient of long-range repellent and attraction
Contact adhesion and repulsion
Growth cone senses and integrates signals
83
What is the corpus callosum?
Largest fibre tract in brain
| Formed by axons projecting to opposite hemisphere
84
What do axon guidance defects result in?
Complete or partial failure of corpus callosum to form
85
What are the symptoms of agenesis of the corpus callosum?
```
Variable severity
Sensory and motor deficits including:
- Vision impairments
- Low muscle tone
- Poor muscle coordination
- Delays in motor milestones
Cognitive disabilities; eg in:
- Complex problem solving
- Missing subtle social cues
```
86
When do gyri and sulci start to develop?
Seven months of gestation
87
What processes in brain development continue or happen after birth?
Axonal and dendritic outgrowth
Synapse formation
Myelination
88
What is the relative rate of development of excitatory and inhibitory synapses?
Excitatory synapses peak a lot earlier than inhibitory synapses develop
89
What does refinement of of synapses involve?
Connections originally overproduced
Performance improved by adjusting number, boundaries, and strength of connections through competitive process
Eg: poly- to mono-innervation at developing neuromuscular junction
