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Sophie - The Nervous System - Year 2 > 17 Embryonic development (CNS) > Flashcards

17 Embryonic development (CNS) Flashcards

1
Q

What is the embryological origin of neural and glial cells?

A

Neuroectoderm

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2
Q

What is the origin of basal (motor) plate?

A

The ventral (‘lower’) side of the neural tube
So ectoderm

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3
Q

What is the origin of the alar (sensory) plate?

A

The dorsal (‘upper’) side of the neural tube
Ectoderm

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4
Q

What are neural crest cells?

A
  • Cells released from the dorsal lip when the neural tube is closing
    • Neural tube cells undergo epithelial-to-mesenchymal transition (EMT), delaminate and migrate to the periphery
  • These cells are essentially a sea of stem cells that can then migrate and differentiate to form a wide range of cells in the periphery
    • The PNS is derived from neural crest cells
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5
Q

What are the derivatives of NCCs?

A

Neural aspects e.g. ganglia

Melanocytes

Enteric nervous system

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6
Q

Can mature neurons undergo mitosis?

A

No

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7
Q

Where are the sites of adult neurogenesis?

A

Sub-ventricular zone and dentate gyrus.

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8
Q

What are the first three regions of the developing brain that form?

A

Forebrain = prosencephalon
Midbrain = mesencephalon
Hindbrain = rhombencephalon

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9
Q

What are the 5 secondary vesicles the 3 primary vesicles? What adult structures do these eventually develop into?

A
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10
Q

What are the different steps of CNS development? (Brief)

A
  • Neural induction
  • Neurogenesis
  • Cell differentiation
  • Differentiation of connections
  • Specialisation within the CNS
  • Early spontaneous activity within the CNS
  • Sensory connectivity patterns
  • Plasticity
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11
Q

What is neural induction? (Brief)

A
  • This is where the CNS is developed from the neural plate
  • The plate closes to form the neural tube
    • This tube is patterned in a longitudinal and ventral/dorsal pattern
    • Longitudinal patterning by Hox genes
    • Ventral/dorsal patterning by interactions from the surrounding mesoderm
  • The rostral end of the neural tube forms the telencephalic vesicles, including the cerebral cortex (largest part of the brain)
  • This process is linked to and occurs shortly after gastrulation
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12
Q

What occurs prior to neural induction?

A
  • Fertilised egg divides and then invades the endometrium of the uterus
  • The placenta, bilaminar and eventually trilaminar disc is formed
    • Trilaminar disc is formed during gastrulation
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13
Q

What is gastrulation?

A
  • This is the conversion of the bilaminar disc (made up of hypoblast and epiblast) into the trilaminar disc (mesoderm, endoderm and ectoderm)
  • Cells migrate between the two primitive layers via the primitive streak - the cells that migrate become the mesoderm
    • Some of the primitive mesodermal cells migrate below the hypoblast to form the neural plate
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14
Q

What is the neural plate and how does it develop?

A
  • The neural plate is a thickening made up of ectoderm, and lies opposing the primitive streak (formed from migrating primitive mesodermal cells)
  • Neural plate develops after the inducing effect of the primitive streak and is the basis of the nervous system
  • Formation of nervous tissue involved complex interactions between mesoderm and ectoderm, mediated by:
    • Shh and noggin
    • BMPs, wnt, FGFs
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15
Q

What germ layer forms the nervous tissue?

A

Ectoderm

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16
Q

How is the eye formed?

A
  • As an outgrowth of the CNS (specifically the diencephalon)
    • This includes the retina, optic nerve and tract
  • This means that the eyes are part of the CNS
  • A cup is formed with inner and outer layers
    • Inner layer gives rise to the neuroretina
    • Outer layer gives rise to the pigment epithelium
    • [EXTRA] Retinal detachment occurs directly at this embryonic boundary
  • The subarachnoid space extends to the optic disc
    • [CLINICAL] This means that intercranial pressure can cause the optic disc to protrude into the eye, so can be measured by looking at the papilla using an ophthalmoscope
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17
Q

How does the ventricular system develop?

A
  • These are formed from dilation of the space within the neural tube
  • Start simple, but become more and more complex until their characteristic shape is obtained
    • Eventually forms two lateral ventricles, the third ventricle, the cerebral aqueduct and the fourth ventricle
18
Q

What are the different structures within the embryonic forebrain, midbrain and hindbrain?

A
  • Forebrain
    • Telencephalon (cerebral hemispheres)
    • Diencephalon (anterior forebrain structures, including thalamus, hypothalamus, posterior pituitary, pineal gland)
    • Neural retina
    • Lens
    • (Lateral ventricle and 3rd ventricle)
  • Midbrain
    • Mesencephalon (all midbrain structures, e.g. colliculi, tegmentum, cerebral peduncles)
    • (Cerebral aqueduct)
  • Hindbrain
    • Metencephalon (pons and cerebellum)
    • Meyelencephalon (medulla)
    • (4th ventricle)
19
Q

What is the signalling centre for ventro-dorsal patterning? What is established by this patterning?

A
  • Notochord - this is a signalling centre outside of the CNS, and is of mesodermal origin, using Shh as a signalling molecule
  • Notochord induces the floor plate, which induces further differentiation along the neural tube
  • Patterning also allows the establishment of motor neuron pools (somatic motor and visceral)
20
Q

What structure does the notochord induce in the neural tube?

A

Floor plate (FP), which lies ventrally, using Shh

21
Q

What does the floor plate do?

A
  • Induces further differentiation throughout the neural tube
    • This is not limited to the spinal cord but also extends to the brainstem and base of the telencephalic vesicle
22
Q

What is the roof plate (RP)?

A
  • Thickening on the dorsal side of the neural tube
  • Expresses BMP4 to effect development of neurons
    • Specifically induces the formation of commissural interneurons (decussating interneurons)
  • Dorsal side contains sensory (somatic and visceral) nerve fibres
23
Q

Is embryonic patterning of the spinal cord retained in the adult?

A

Yes, roughly

24
Q

What does rostro-caudal patterning depend on?

A

Depends on the dimensions and signals from the rhombomeres, and the location of the nulcei
WNT

25
Q

What cells facilitate neurogenesis?

A
  • Neuroepithelium generates neurons at a very high rate
  • Progenitor cells (therefore partially restricted) are found within the neuroectoderm
26
Q

Where do most of the divisions in neurogenesis occur?

A

Next to the ventricular zones/CSF-filled ventricles

27
Q

What happens after neurogenesis?

A
  • Cells then migrate out towards the pial surface/towards the skull
  • The first post-mitotic cells are found at this surface, which is known as the primordial plexiform zone or ‘pre-plate’
  • This patterning method is the same within all mammals, with projenitors in the ventricular zone/subventricular zone and mature post-mitotic cells lying close to the pial membrane/pre-plate region
  • This migration route starts short but eventually grows longer
28
Q

What is the patterning of neurogenesis?

A
  • This method of patterning is the same within all mammals, with progenitors in the VZ (ventricular zone) and SVZ (subVZ), with mature post-mitotic cells being observed close to the pial membrane/in the pre-plate region – the route starts short and then increases in length
  • This is initially split into two regions (marginal zone and the sub-plate), then the cortical plate develops from an inner- to outermost fashion between the two, largely transient cell layers.
29
Q

What is Spina Bifida?

A

Spina Bifida → failure of neural tube to close at caudal end
Spectrum
SB occulta → incomplete posterior closure of the vertebrae
SB meningocele → protrusion of the meninges
SB myelomeningocele → protrusion of the spinal cord itself.
Often associated w/ severe disability
Even w/ occulta can have lower limb weakness + sensory deficits

30
Q

What is taken during pregnancy to prevent spina bifida?

A

MTC vitamin study research group (1991) → showed folic acid supplementation ↓ incidence of neural tube defects in high-risk pregnancies by 72%
Folic acid supplementation now recommended to all women trying to conceive or before W12 of gestation.

31
Q

Why is cell migration important in CNS development?

A

Neurons generated in ventricular zone must migrate to their final destination

32
Q

What are the two main types of migration?

A

*Radial migration
*Tangential migration

33
Q

Describe how radial migration takes place.

A

1st wave migrates independently of glia (via somal translocation)
*Extend leading processes that attach to pial surface. Nucleus then moves through cytoplasm via nucleokinesis. Trailing processes retracted from ventricular surface.
*Involved simplex molecular machinery (actin/ microtubules/ filamin)

Subsequent waves (90% of migrating neurons in humans) use bipolar RGCs as scaffold.
*Migrating neurons attach processes to BRGCs to guide them into developing cortical plate.

34
Q

Which neurons use radial migratioon?

A

Glutamatergic neurons

35
Q

Describe tangential migration.

A

*Move parallel to surface of brain
*Interneurons disperse from ganglionic eminences (GEs) in ventral forebrain to rest of brain.
*Precursor cells from different GEs supply different regions of dev brain:
*Medial GEs → dorsally into neocortex
*Lateral GEs → anteriorly into olfactory bulb
*Involved axonal guidance/ leading process extension/ nucleokinesis/ stop signal

36
Q

Which neurons use tangential migration?

A

GABAergic

37
Q

How are neural connections established?

A
  • If there are lots of projections extending from one region of the brain to another, they have to interconnect in a topographic way/organised manner
    • Some rely upon molecular cues to reach their final destination, whereas a small proportion are able to find their way using neuronal activity
  • The axons and cells extend long neurites that are able to navigate within the environment through the use of growth cones
  • Connections are usually established when the distance between cells is minimal
  • The growth cone exists on the tip of the advancing neuron, using filopodia to explore the immediate environment (look like flickering fingers)
    • There is actin polymerisation occurring within these filopodia (can be visualised using GFP)
  • There is local attraction and repulsion, the insertion of new cytoskeleton and autonomous action
  • Growth cones respond to various positive and negative cues (e.g. contact, distance, diffusible chemicals)
38
Q

How are axons thought to be guided to their correct connections?

A
  • Using molecular cues - growth cones are either attracted or repelled by these
    • These cues can be local (substrate-bound) or long-range (diffusible)
  • A given molecule can be both attractive and repulsive, depending on the interaction
39
Q

What are the final stages of neuronal patterning driven by?

A

*Cell death
*Establishment of neuronal connections
*Synaptic plasticity

40
Q

Why is neuronal cell death important?

A

Neuronal cell death imp at subplate of intermediate zone.
Facilitates loss of dynamic + transient scaffold (for organised migration)
*Vulnerable to dev. defects

To increase the efficiency of existing connections as axons and dendrites link up

41
Q

What controls differentiation of neuronal precursors into their subtypes?

A

Different growth factors
e.g. SOX5 in the subplate layer

Sophie - The Nervous System - Year 2 (46 decks)

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