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Development p1 Flashcards

1
Q

What is neural induction

A

The process where embryonic cells in the ectoderm are induced to acquire a neural fate, forming the neural plate

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2
Q

What does the neural plate eventually give rise to

A

Central and peripheral nervous system

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3
Q

What is gastriulation

A

Creation of a gastrula, forming the 3 distinct germ layers

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4
Q

What is the important organising centre that controls neural induction

A

The dorsal blastopore lip of the gastrula

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5
Q

What did Spemann and Mangold show the dorsal blastopore lip of the gastrula induces

A

The formation of a body axis

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6
Q

What does the dorsal blastopore lip later form

A

The dorsal mesoderm

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7
Q

What study did Spemann and Magold do

A

Transplanting a second dorsal blastopore lip into a salamander gastrula induces host tissue to form a secondary body axis -> entre nervous system

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8
Q

What is the ‘default’ fate of ectoderm cells in neural induction

A

Neural diffentiation

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9
Q

What do proteins secreted by the dorsal blastopore lip

A

Act as BMP antagonists, de-repressing neural differentiation

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10
Q

What prevents ectoderm cells achieving their ‘default’ neural differentiation fate

A

Neighbouring ectoderm cells synthesize and secrete BMPs, suppressing potential for neural differentiation and promoting epidermal differentiation instead

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11
Q

What are examples of proteins secreted by the dorsal blastopore lip that act as BMP antagonists

A

Noggin, Wnt chordin, follistatin

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12
Q

What chemicals act as intermediaries in neural differentiation (Pankratz)

A

Transcriptino factors of the SoxB family, expressed in prospective neural plate cells

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13
Q

What growth factors are necessary for neural differentiation other than BMP antagnosist

A

Ectoderm cells must be exposed to fibroblast growth factors

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14
Q

What results from disorders of neural induction

A

Abnormalities in forming the body axus can cause dicephalic parapagus- a rare form of conjoined twins

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15
Q

What is neural patterning

A

Process by which cells in the developing nervous system acquire distinct identities according to their specific spatial positions

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16
Q

What do the rostral vs caudal regions of the neural plate secrete

A

Mesoderm in caudal regions- high Wnt levels

Endoderm in rostral region- proteins that inhibit Wnt

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17
Q

What gradient controls rostral caudal patterning in the neural plate

A

Gradient of Wnt- high at caudal, low at rostral

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18
Q

What additional signals refine the rostrocaudal pattern other than Wnt gradient

A

Anterior neural ridge (ROSTRAL)- secretes FGF, forms telencephalon
Mesoderm at CAUDAL levels- secretes retinoic acid and FGF, forms subdomains of hindbrain and spinal cord

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19
Q

What 2 specialised cell groups in the neural tube refine the ROSTROCAUDAL PATTERN

A

Zona limitans intrathalamica (diencephalon), isthmic organiser (hind/mid brain boundary)

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20
Q

What does the zona limitans intrathalamica do

A

Secretes sonic hedgehog that causes nearby cells to form thalamic nuclei

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21
Q

What does the isthmic organiser do

A

Specifies the neuronal subtypes within the hind- and mid- brain ie DA neurons in midbrain, 5HT neurons in hindbrain
Secretes Wnt 1 and FGF8

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22
Q

Describe the different domains either side of the midbrain-hindbrain boundary

A

Cells either side express different Hox genes and different homeodomain transcription factors, that control the expression of signalling factors like Wnt, FGF, Shh

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23
Q

Describe the role of Hox genes in rostrocaudal patterning

A

Rostrocaudal differences in Hox gene expression determine the identity of neurons in different rhombomeres

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24
Q

What are rhombomeres

A

Rostrocaudal segments of the developing hindbrain

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25
What develops from the different rhombomeres
Different cranial nerves emerge from each rhombomere
26
What type of cells form from the dorsal neural tube
Sensory neurons, local circuit interneurons, neural crest cells
27
What type of cells form from the ventral neural tube
Motor neurons and interneurons
28
What provides ventral patterning signals
First notochord, then floorplate
29
What is the notochord
Mesodermal cells group directly under the ventral neural tube
30
What provides dorsal patterning signals
First epidermal ectoderm spanning the dorsal midline, then the roof plate
31
What are the roof and floor plate
Glial cell groups
32
What do the notorchord and floor plate secrete for ventral patterning
Sonic hedgehog
33
What is sonic hedgehog
A morphogen- can direct different cell fates at different concentrations
34
What gradients determine ventral patterning
Ssh ventral->dorsal gradient in the ventral area | Corresponding gradient of Gli transcription factor
35
What is Gli transcriptino factor
Usually prevents Shh activation
36
What is the result of the Ssh Gli ventral gradient
Different homeodomain transcriptino factors repressed in different regions -> different differentiation -> 5 cardinal progenitor domains and 5 classes of ventral neurons
37
What occurs first in dorsal patterning
Epidermal cells in the midline release BMP4, which triggers differentiation of root plate
38
What occurs in dorsal patterning once the neural tube closes
Roof plate cells express BMP and Wnt proteins eg BMP4
39
What does BMP4 do when secreetd by the roof plate
Induces differentiation of neural crest cells, then generation of sensory neurons
40
What does Wnt protein do when secreted by the roof plate
Promotes proliferation of progenitor cells in the dorsal neural tube
41
What is neurulation
The folding of the neural plate into the neural tube
42
Examples of mechanisms invovled in neurulation
Transcription regulation, proteases, antagonistic interactions between BMPs/SSh/Noggin
43
What disorders result from mutations in the Shh dorsoventral pathway
Defects in ventral forebrain structure development, spina bifida, limb deformities, cancer
44
What is spina bifida
Spine and spinal cord don't form properly, neurulation messed up
45
What disorders result from the caudal end of the neural tube not closing properly
Spinal dysraphism (conditinos affecting the spine/spinal cord/nerve roots) eg spina bifida
46
What disorders result from the rostral end of the neural tube nto closing properly
Anencephaly, inionschisis
47
What is anencephaly
Absense of a major portion of te brain, skull and scalp
48
What is inionschisis
Failure of the neural tube to close in the occipital region
49
What region is involved in generating neural cells
Proliferative zones surrounding the ventricles
50
What are progenitor cells
Cells in the vetricular zone of the neural tube, proliferate rapidly in early embryonic development, have stem cell-like properties
51
What is asymmetrical cell division
Progenitor produces a daughter that retains cell-like properties, and one differentiated daughtter
52
What is symmetrical cell division
neural stem cells divide to form 2 stem cells, expanding the population of proliferative progenitor cells
53
What are radial glial cells
The earliest distinguishable cell type in the neural epithelium, progenitor cells
54
What can radial glial cells do
Generate neurons and astrocytes, undergo asymmetric and self-renewing cell division
55
Describe how the different parts of radial glial cells are spread out
Cell bodies in the vetricular zone, long-processes end in the pial surface- remain attached to these surfaces as the brain thickens
56
How are radial glial cells important in cell migration
Serve as a scaffold for the migratino of neurons emerging from the ventricular zone
57
What cell-surface signallingsystem determines the fate of radial glial cells
Involves transmembrane ligand delta and its receptor Notch, which regulate a cascade of basic helix-loop-helix transcription factors
58
What happens to radial glial cells with low vs high Notch activation
LOW- neurons | HIGH- radial glial cells, astrocyctes, oligodendrocytes
59
What antagonises Notch signalling
Numb, a cytoplasmic protein that antagonises Notch signalling
60
What does Numb do
Expressed in neuronal daughters of dividing progenitors, allows glial cells to avoid exposure to Notch signals, and develop into neurons
61
What are the 3 main stages of cerebral cortex development
Preplate, cortical plate, mature pattern of layers
62
Describe how neurons migrate along radial glial fibres
Neurons in the preplate extend a leading process to wrap around the radial glial cell, settling in the cortical plate
63
What happens in cerebrla cortex migration once the cortical plate is formed
Neurons continue migrating, forming cortical layers in an inside-first, outside-last way
64
What other ways can cells migrate than using radial glial cells
Can migrate using pre-existing axonal tracts, neural crest cells undergo free migration throughout the body
65
What are filopodia
Extensions from growth cones, detect attractive/repellant directional cues from the environment with surface receptors
66
How do growth cones respond to directional cues
Transduce these cues into signals that regulate their cytoskeleton, acting as motor structres to drive axon elongation
67
What can intracellular signals in the growth cone do
Alter the growth cone's response to growth factors as either attractor or repellant
68
What proportion of neurons generated in the nervous system are lost
Half
69
What is the neurotrophic factor hypothesis
Cells at a neuron's target site secrete a small amount of a trophic factor, uptake by a neuron suppresses a latent death program in that neuron
70
How are cells programmed to die without neurotrophic growth factor
Apoptosis
71
How do neurotrophins work
Bind to receptors on nerve terminals, internalised, activate signalling pathways and transcription programs necessary for survival
72
What disorder can issues duringc cell generation cause
Microcephaly- baby's brain does not develop properly, causing small head
73
What disorders can defective neuronal migration cause
Lissencephaly, periventricular heterotrophia
74
What is periventricular heterotopia
Neurons don;t migrate properly, form clumps around the ventricules
75
How does the eye develop from the diencephalon
Inner layer-> neural retina Outer layer-> pigmented epithelium Subarachnoid space extends to the optic disk
76
What substance presumbly prevents spina bifida
Folic acid
77
What are homeotic genes
Genes that, when mutated, cause conversino of one part of the body into another
78
Zika?
Zika causes microcephaly/corpus callosum agenesis/lissencephaly IF caught by mama in the first trimester
79
What are sites of adult neurogenesis
Subventricular zone, dentate gyrus
80
What things suggest our neurons are the very old
No mitosis of mature neurons, very limited neurogenesis in cerebral cortex, limited sites of adult neurogenesis
81
What are the 2 major areas of tangential migration
Neurons in the medial ganglion eminence migrate to the neocortex to form interneuron populations Neurons in the lateral ganglion eminence migrate rostrally to contribute to interneurons of the olfactor bulb
82
How do neural crest cells first leave the neural tube
BMP signalling causes cells to break down the basement membrane surrounding the neural tube epithelium, and delaminate from the neural tube
83
What internal change happens to neural crest cells ocne they delaminate from the neural tube
Cell adhesino protein expression changes, meaning they lose adhesive contacts with neural tube cells Begin to express integrins, receptors for proteins found along migratory paths
84
What path do neural crest cells take towards the periphery
Pass through the anterior half of somites, as proteins in their posterior half repel them- some remain here OR some go dorally around the somite
85
What happens to neural crest cells that stay in the anterior somite half
Differentiate into sensory neurnos of the DRG, dependent on Wnt signals and bHLH factors
86
What happens to neural crest cells that go dorsally aruond the somite
These cells are exposed to BMPs and develop as symapthetic NA neurons
87
What does the endoderm give rise to
Gut tube, lungs, pancreas, liver
88
What does the mesoderm give rise to
Muscle, connective tissues, vasulcar system
89
What does the ectoderm give rise to
Skin, neural plate
90
What do somites give rise to
Muscle and cartilage
91
What transcriptino factors are expressed in the forebrain/midbrain vs hind brain
Forebrain/midbrain- Otx2 | Hindbrain- Gbx2

Neurophysiology (23 decks)

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