1: Morphogenesis of the Brain Flashcards

1
Q

*What are the primary and secondary brain vesicles? (3 primary, 5 secondary)

A

Primary vesicles: [caudal to rostral]

  1. Rhombencephalic vesicle - level of brainstem
  2. Mesencephalic vesicle - level of midbrain
  3. Prosencephalic vesicle - most rostral

Secondary vesicles: [caudal to rostral]

  1. Myelencephalon (from rhombencephalic)
  2. Metencephalon (from rhombencephalic)
  3. Mesencephalon (from mesencephalic)
  4. Diencephalon (from prosencephalic)
    - Has optic vesicles, which -> retinas
  5. Telencephalon (from prosencephalic)
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2
Q

*What does each secondary vesicle become in the adult?

A

Metencephalon and myelencephalon -> 4th ventricle
Mesencephalon -> cerebral aqueduct
Diencephalon -> 3rd ventricle
Telencephalon -> lateral ventricles

Cerebellum grows from lateral parts of metencephalon

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3
Q

*What are the primary bends in the neural tube? What do they separate? (2)

A

Cervical flexure: separates developing spinal cord and brainstem

Cephalic flexure: at level of midbrain

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4
Q

*What are the alar and basal plates? How are these organized in the spinal cord and brain?

A

Alar plate -> dorsal horn; involved in sensory processing
-Becomes lateral in brainstem (sensory = lateral)
Basal plate -> ventral horn; contains motor neurons
-Becomes medial in brainstem (motor = medial)

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5
Q

*What are the layers of the developing neural tube? What happens in each?

A

Ventricular zone: where everything starts out

Mantle zone: where post-mitotic cells migrate to
-Send out axons to periphery -> marginal zone

Mantle zone = gray matter, marginal zone = white matter

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6
Q

While the neural tube is expanding, what are the cells of the neural tube doing?

A

Rapidly dividing!

Maintain connection with lumen of neural tube and pial surface

Bounce back and forth between the pial surface (S phase) and the neural tube lumen surface (M phase of mitosis)

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7
Q

*What causes a “bouncing” neuroblast to stop dividing?

A

Neuroblasts have notch-1 concentrated in apical portion and numb concentrated in basal portion

Mitosis along pole -> cells keep dividing (have notch and numb)

Mitosis along equator -> one cell has notch I (no numb) -> stops dividing -> migrates to pial surface -> forms mantle zone
-Other cell (with numb) makes notch, keeps dividing

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8
Q

*What factors regulate whether a cell will be a neuron or glial cell? Describe the concept of lateral inhibition.

A

Notch and delta (another surface marker) are mutually inhibitory, in delicate balance
If balance -> more notch, cell -> glioblast
If balance -> more delta, little notch, activated bHLH genes, cell -> neuroblast

Adjacent cells affected by neighbors (LATERAL INHIBITION): one cell -> neuron, adjacent -> glia and so on (ensure balanced production)

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9
Q

*What layer develops first in the cortex? Which layer is second? (continue)

A

This is INSIDE OUT cortical development

1st: Layer I, part of the marginal zone
2nd: Layer VI, follows radial glia to layer I and stops below it
3rd: Layer V, follows radial glia to layer I and stops below it, displacing layer VI
4th: Layer IV (same)
5th: Layer III (same)
6th: Layer II (same)

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10
Q

What factor is critical for normal migration? What cells secrete it?

A

Reelin

From Cajal-Retzius cells

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11
Q

*What are radial glia and what do they do?

A

Radial glia: glial cells that establish connection from the ventricular surface all the way to the pial surface

Neuroblasts crawl along them to migrate up to the pial surface

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12
Q

*What is formed by the neural crest cells? (4 neuronal, 3 non-neural)

A

Neuronal things (4): all elements of PNS except somatic/preganglionic autonomic motor axons

  • DRG, sensory nerve fibers
  • Ganglia of cranial nerves
  • Autonomic ganglia
  • Adrenal medulla

Non-neural things (3)

  • Schwann cells, satellite cells
  • Leptomeninges (pia/arachnoid)
  • Bone and CT of face and most of the skull
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13
Q

*What factors determine if a neural tube will develop from ectoderm?

A

Neural tube development induced by INHIBITION of bone morphogenic proteins (BMPs) by presence of noggin and chordin from notochord

Normally, BMP secreted by ectoderm, prevents ectoderm from -> neuroectoderm
Noggin and cordin from notochord bind BMP, block its effect on region to become neural tube

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14
Q

What do all factors that differentiate portions of the nervous system from one another have in common?

A

All affect nuclear transcription

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15
Q

*What factors differentiate ventral from dorsal part of the neural tube?

A
Sonic hedgehog (Shh) ventrally (from notochord and then from floorplate)
TGF betas dorsally (BMP, dorsalin, retinoic acid, noggin)

Shh most important!

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16
Q

How does Shh function? What factor is required for its proper diffusion and activity?

A

Patched (receptor) inhibits smoothened (another receptor)
Shh acts on patched, prevents inhibition of smoothened -> smoothened activates a family of ventralizing TFs

Cholesterol is required, therefore statins are severely teratogenic to developing brain

17
Q

*What diffusible compounds determine the level of the brain stem that will develop from a particular part of the neural tube?

A

Retinoic acid is concentrated in cervical area and diffuses
Conveys a CAUDAL identity
Downstream targets include Hox genes, which are expressed based on retinoic acid concentration

18
Q

Why are certain acne drugs teratogenic?

A

They are analogs of retinoic acid

Can severely disrupt rostral-caudal development by exposing developing brainstem to retinoic acid

19
Q

*What factors determine the fate of neuroblast as it develops?

A

Cells are affected by the milieu through which they migrate

Various growth factors in areas cells reside/migrate through are likely to be the main determinant factors in what kind of cell the neuroblast will become

20
Q

Briefly describe the process of neurulation.

A

Thickening of ectoderm in midline above notochord -> neural plate -> neural groove (floorplate + neural crest) -> zipping closure of neural groove -> neural tube with central canal -> migration/differentiation

21
Q

What is anencephaly?

A

Anterior neuropore fails to close

Incompatible with life

22
Q

What is spina bifida? How can it be prevented?

A

Failure or delay in closure of the posterior neuropore
Spina bifida occulta = minor
Meningocele/meningomyelocele/spinal cord open on back = severe
Prevented via intake of folic acid

23
Q

What is holoprosencephaly?

A

Cyclopeia accompanied by a single large brain ventricle

Results from defects in Shh signaling -> disruption of ventral/dorsal differentiation

24
Q

What causes the brain to grow and change shape after the migration of cortical neurons?

A

Changes in the cerebral cortical dendritic and axonal complexity

25
Q

What happens to neurons that don’t make appropriate connections?

A

Apoptosis

As many as 80-90% of neurons in some areas