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Neurophysiology > Development p1 > Flashcards

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
Q

What develops from the different rhombomeres

A

Different cranial nerves emerge from each rhombomere

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26
Q

What type of cells form from the dorsal neural tube

A

Sensory neurons, local circuit interneurons, neural crest cells

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27
Q

What type of cells form from the ventral neural tube

A

Motor neurons and interneurons

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28
Q

What provides ventral patterning signals

A

First notochord, then floorplate

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29
Q

What is the notochord

A

Mesodermal cells group directly under the ventral neural tube

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30
Q

What provides dorsal patterning signals

A

First epidermal ectoderm spanning the dorsal midline, then the roof plate

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31
Q

What are the roof and floor plate

A

Glial cell groups

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32
Q

What do the notorchord and floor plate secrete for ventral patterning

A

Sonic hedgehog

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33
Q

What is sonic hedgehog

A

A morphogen- can direct different cell fates at different concentrations

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34
Q

What gradients determine ventral patterning

A

Ssh ventral->dorsal gradient in the ventral area

Corresponding gradient of Gli transcription factor

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35
Q

What is Gli transcriptino factor

A

Usually prevents Shh activation

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36
Q

What is the result of the Ssh Gli ventral gradient

A

Different homeodomain transcriptino factors repressed in different regions -> different differentiation -> 5 cardinal progenitor domains and 5 classes of ventral neurons

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37
Q

What occurs first in dorsal patterning

A

Epidermal cells in the midline release BMP4, which triggers differentiation of root plate

38
Q

What occurs in dorsal patterning once the neural tube closes

A

Roof plate cells express BMP and Wnt proteins eg BMP4

39
Q

What does BMP4 do when secreetd by the roof plate

A

Induces differentiation of neural crest cells, then generation of sensory neurons

40
Q

What does Wnt protein do when secreted by the roof plate

A

Promotes proliferation of progenitor cells in the dorsal neural tube

41
Q

What is neurulation

A

The folding of the neural plate into the neural tube

42
Q

Examples of mechanisms invovled in neurulation

A

Transcription regulation, proteases, antagonistic interactions between BMPs/SSh/Noggin

43
Q

What disorders result from mutations in the Shh dorsoventral pathway

A

Defects in ventral forebrain structure development, spina bifida, limb deformities, cancer

44
Q

What is spina bifida

A

Spine and spinal cord don’t form properly, neurulation messed up

45
Q

What disorders result from the caudal end of the neural tube not closing properly

A

Spinal dysraphism (conditinos affecting the spine/spinal cord/nerve roots) eg spina bifida

46
Q

What disorders result from the rostral end of the neural tube nto closing properly

A

Anencephaly, inionschisis

47
Q

What is anencephaly

A

Absense of a major portion of te brain, skull and scalp

48
Q

What is inionschisis

A

Failure of the neural tube to close in the occipital region

49
Q

What region is involved in generating neural cells

A

Proliferative zones surrounding the ventricles

50
Q

What are progenitor cells

A

Cells in the vetricular zone of the neural tube, proliferate rapidly in early embryonic development, have stem cell-like properties

51
Q

What is asymmetrical cell division

A

Progenitor produces a daughter that retains cell-like properties, and one differentiated daughtter

52
Q

What is symmetrical cell division

A

neural stem cells divide to form 2 stem cells, expanding the population of proliferative progenitor cells

53
Q

What are radial glial cells

A

The earliest distinguishable cell type in the neural epithelium, progenitor cells

54
Q

What can radial glial cells do

A

Generate neurons and astrocytes, undergo asymmetric and self-renewing cell division

55
Q

Describe how the different parts of radial glial cells are spread out

A

Cell bodies in the vetricular zone, long-processes end in the pial surface- remain attached to these surfaces as the brain thickens

56
Q

How are radial glial cells important in cell migration

A

Serve as a scaffold for the migratino of neurons emerging from the ventricular zone

57
Q

What cell-surface signallingsystem determines the fate of radial glial cells

A

Involves transmembrane ligand delta and its receptor Notch, which regulate a cascade of basic helix-loop-helix transcription factors

58
Q

What happens to radial glial cells with low vs high Notch activation

A

LOW- neurons

HIGH- radial glial cells, astrocyctes, oligodendrocytes

59
Q

What antagonises Notch signalling

A

Numb, a cytoplasmic protein that antagonises Notch signalling

60
Q

What does Numb do

A

Expressed in neuronal daughters of dividing progenitors, allows glial cells to avoid exposure to Notch signals, and develop into neurons

61
Q

What are the 3 main stages of cerebral cortex development

A

Preplate, cortical plate, mature pattern of layers

62
Q

Describe how neurons migrate along radial glial fibres

A

Neurons in the preplate extend a leading process to wrap around the radial glial cell, settling in the cortical plate

63
Q

What happens in cerebrla cortex migration once the cortical plate is formed

A

Neurons continue migrating, forming cortical layers in an inside-first, outside-last way

64
Q

What other ways can cells migrate than using radial glial cells

A

Can migrate using pre-existing axonal tracts, neural crest cells undergo free migration throughout the body

65
Q

What are filopodia

A

Extensions from growth cones, detect attractive/repellant directional cues from the environment with surface receptors

66
Q

How do growth cones respond to directional cues

A

Transduce these cues into signals that regulate their cytoskeleton, acting as motor structres to drive axon elongation

67
Q

What can intracellular signals in the growth cone do

A

Alter the growth cone’s response to growth factors as either attractor or repellant

68
Q

What proportion of neurons generated in the nervous system are lost

A

Half

69
Q

What is the neurotrophic factor hypothesis

A

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
Q

How are cells programmed to die without neurotrophic growth factor

A

Apoptosis

71
Q

How do neurotrophins work

A

Bind to receptors on nerve terminals, internalised, activate signalling pathways and transcription programs necessary for survival

72
Q

What disorder can issues duringc cell generation cause

A

Microcephaly- baby’s brain does not develop properly, causing small head

73
Q

What disorders can defective neuronal migration cause

A

Lissencephaly, periventricular heterotrophia

74
Q

What is periventricular heterotopia

A

Neurons don;t migrate properly, form clumps around the ventricules

75
Q

How does the eye develop from the diencephalon

A

Inner layer-> neural retina
Outer layer-> pigmented epithelium
Subarachnoid space extends to the optic disk

76
Q

What substance presumbly prevents spina bifida

A

Folic acid

77
Q

What are homeotic genes

A

Genes that, when mutated, cause conversino of one part of the body into another

78
Q

Zika?

A

Zika causes microcephaly/corpus callosum agenesis/lissencephaly IF caught by mama in the first trimester

79
Q

What are sites of adult neurogenesis

A

Subventricular zone, dentate gyrus

80
Q

What things suggest our neurons are the very old

A

No mitosis of mature neurons, very limited neurogenesis in cerebral cortex, limited sites of adult neurogenesis

81
Q

What are the 2 major areas of tangential migration

A

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
Q

How do neural crest cells first leave the neural tube

A

BMP signalling causes cells to break down the basement membrane surrounding the neural tube epithelium, and delaminate from the neural tube

83
Q

What internal change happens to neural crest cells ocne they delaminate from the neural tube

A

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
Q

What path do neural crest cells take towards the periphery

A

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
Q

What happens to neural crest cells that stay in the anterior somite half

A

Differentiate into sensory neurnos of the DRG, dependent on Wnt signals and bHLH factors

86
Q

What happens to neural crest cells that go dorsally aruond the somite

A

These cells are exposed to BMPs and develop as symapthetic NA neurons

87
Q

What does the endoderm give rise to

A

Gut tube, lungs, pancreas, liver

88
Q

What does the mesoderm give rise to

A

Muscle, connective tissues, vasulcar system

89
Q

What does the ectoderm give rise to

A

Skin, neural plate

90
Q

What do somites give rise to

A

Muscle and cartilage

91
Q

What transcriptino factors are expressed in the forebrain/midbrain vs hind brain

A

Forebrain/midbrain- Otx2

Hindbrain- Gbx2

Neurophysiology (23 decks)

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