03-21 Morphogenesis; Wiring

Question 1

What are the primary and secondary brain vesicles? What does each vesicle become in the adult?

Answer 1

The primary vesicles (from rostral to caudal) are:

• prosencephalic
  
  • 2°
    
    • most rostral - telecephalon from lateral outpouchings -> lateral ventricles
    • just caudal - diencephalic -> 3rd ventricle
• mesencephalic
  
  • beceomes cerebral aqueduct
• rhombencephalic
  
  • 2° - pontine flexure:
    
    • myencephalon (caudal portion of 4th ventrical i.e. the medulla)
    • metencephalon (rostral part of the 4th ventricle i.e. the pons)

Question 2

What are the primary bends in the neural tube? What do they separate?

Answer 2

the pontine flexure seperates the rhombencephalon into metencephalon and myelencephalon

the cervical flexure separates the prosencephalon into the telencephalon and the diencephalon

Question 3

What are the layers of the developing neural tube?

What happens in each?

Answer 3

Ventrical layer - stays thin and lines the ventricles becoming the ependymal layer

Mantle layer - cells grow out, following radial glia into the mantle region; becomes the spinal gray matter post-migration

Marginal layer - axons from the cells in the mantle layer grow out into the marginal layer; becomes the spinal white matter post-migration

Question 4

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

Answer 4

basal are ventral; contain mostly motor neurons

alar are dorsal; contain mostly sensory neurons

the are separated by the sulcus limitans

Question 5

Which layer develops first in the cortex? Which is second…etc?

Answer 5

1, then 6 then 5…etc.

Therefore 1 is the oldest and 2 is the youngest

This only happens in the brain (where there is actually a cortex)

Question 6

What are radial glia and what do they do?

Answer 6

Radial glia span from the verticlular zone to the marginal zone. The developing waves of neurons follow the processes of the radial glial outward during development.

Question 7

What is formed by the neural crest cells?

Answer 7

• Much of the PNS (including all of the sensory neurons, the pre-synaptic sympathetics, Schwann cells, and the supporting cells of the ganglia)
• Chromaffin cells (in the adrenal medulla)
• Melanocytes
• Development of the outer eye layers and many of the skull bones

Question 8

What factors determine whether the neural tube will develop from ectoderm?

Answer 8

You have to inhibit BMP in ectoderm (bone morphogenic protein, a member of the TGF-ß family)–which are constitutively expressed by ectoderm cells–with noggin, chordin and folistatin from notochord in order to get neural tube differentiation.

Question 9

What factors differentiate the ventral from the dorsal sides of the neural tube?

Answer 9

ventrally: shh (sonic hedgehog)
dorsally: TGF-ß family proteins (e.g. retinoic acid, BMP, dorsalin)

Question 10

In which direction does retinoic acid diffuse? what does it affect?

Answer 10

It diffuses rostrally from the cervical area intro the developing. It affects the expression of hox genes. (This is why pregnancy women can’t take Rx isotretinoin.)

Question 11

What does Notch 1 do?

Answer 11

Notch I (in the absence of numb) causes a neuron to stop dividing.

Question 12

What factors regulate whether a cell will be a neuron or glial cell?

Answer 12

All neuroectoderm will become either neuroblast or glioblasts

Notch prots interacting with delta prots will prevent cells from becoming neuroblasts

Question 13

What does the cerebellum develop from?

Answer 13

the dorsal lips of the metencephalon (which develops when the rhombencephalon is divided in half by the pontine flexure)

Question 14

What does the cavity in the neural tube become?

Answer 14

the ventricular system

Question 15

On what days does the neural tube form

Answer 15

Days 20-28

Question 16

Why are statins contraindicting in pregnancy?

Answer 16

Sonic hedgehog protein require cholesterol for activation

Question 17

From whence do the retinae develop?

Answer 17

Directly from outpouchings of the diencephalon

Question 18

From whence does the inner ear develop?

Answer 18

The inner ear is induced to develop on the ectoderm by the rhombencephalon.

Question 19

BMP

Answer 19

Bone Morphogenic Protein (in TGF-ß family)

Manufactured by the ectoderm; this must be blocked by noggin and chordin in order for ectoderm to become neuroectoderm

Once neural tube is formed, BMP also leads to dorsal development of the neural tube

Question 20

bHLH

Answer 20

Basic helix-loop-helix genes: when activated contribute to the development of a neuron

Question 21

What are the inhibitory neruons in the cortex? Where did the come from? How did they get there?

Answer 21

GABAergic interneurons (usually inhib)

arise from the basal telencephalon (subpallium) which includes that LGE and MGE (lateral/medial ganglionic eminences)

Use tangential migratory routes (i.e. NOT radial migration) guided by the ErbB4 receptors they express binding to Nerugulin 1 gradient

Question 22

What are the excitatory neruons in the cortex? Where did the come from? How did they get there?

Answer 22

Glutamatergic principal cells are excitatory neurons in the cortex

arise from the ventricular zone of the pallium (cortex)

travel via radial migration guided by radial glia

Question 23

Schizophrenia and migration

Answer 23

Many causes, but recent data implicate deficits in Neuregulin-1-to-ErbB4 signalling via fast-spiking GABAergic parvalbumin(Ca2+ binder)-expressing interneurons. This decreases the power of gamma oscillations which are important for cognition, learning and memory.

Question 24

What are the axons connecting the thalamus and the cortex called? What cells guide them in their path? From whence do those cells come?

Answer 24

TCAs (thalamocortical afferents)

corridor cells (GABAergic interneurons) act as guidepost cells which migrate tangentially from the LGE to the MGE forming a permissive corridor for the TCAs to grow through the MGE

*L/G ganglionic eminence

Question 25

What plays the role of guidepost cells in the hippocampus? The cortex?

Answer 25

hippocampus - Cajal-Retzius cells

cortex - floor plate neurons

Question 26

Guidepost cells

Answer 26

cells that express specific
molecules that alter
signaling in growth
cones and change actin
structure to change
growth cone direction

Question 27

How do travelling axons sense guidepost cells’ signals?

Answer 27

growth cones: projections of sheet-like lamellapodia with filipodia projections that sense the environment and change shape and speed in response to environmental cues

differentiate into pre-synaptic termini upon reaching their destination

Question 28

Compare and contrast different types of signal molecules

Answer 28

attractants and repellents

cell/ECM-bound: tend to be short-range police officer directing traffic and right-turns, e.g.

secreted signals: act via inverse gradients for long-range signalling

Question 29

What are the differences between pioneer neurons and “follower” neurons.

Answer 29

pioneers have more elaborate growth cones with many more filipodia

Question 30

trophic vs. tropic molecules

Answer 30

trophic: support growth and survival
tropic: guide migration of neurons

Question 31

Rohon-Beard cells

Answer 31

example of pioneer cells in the spinal cord that also transmit sensory information in the early fetus; undergo programmed cell death

Question 32

Which part of the visual field decussates? Why?

Answer 32

Phew! The dorsal and nasal portions dessucate. (Neurons that originate on the temporal and ventral portions of the retina do NOT dessucate.)

Question 33

Describe the general signaling that allows ECM molecules to guide axons.

Answer 33

interact with integrins on the axons to regulate the text of adhesion of the growth cones and alter the mechanical dynamics that allow growth cones to both extend and pull their axons.

Axons change the number of integrins they express as they grow thus changing their sensitivity to ECM signals along their path.

Question 34

Give a few examples of ECM signal molecules.

Answer 34

laminin, fibronectin

Question 35

Describe how the impact of a single molecule can be switched from attraction to repulsion through the interactions of other extracellular signalling components and their impact on intracellular second messengers.

Answer 35

depends on the concentration of signalling molecules within the growth cone where the molecules act;

for example, as axons from retinal ganglion cells (RGCs) approach the optic chiasm, laminin decreases the levels of cAMP in the growth cones of the axons, this then changes the axons’ relationship to netrin from chemoattractant (which is served as originally to attract the RGC axons to the center of the chiasm in the first place) to chemorepellent

Question 36

Explain how studies in lower vertebrates and invertebrates are relevant to understanding the development of the huiman nervous system.

Answer 36

We have essential the same neurons as lower vertebrates and invertebrates, it’s just that higher vertebrates have vastly largely quantities of neurons and glial cells dramatically increasing the number of permutations the system can have

Question 37

Using the retinotectal (collicular) system, describe the principle (not the specific receptor subtypes) of the chemoaffinity hypothesis and how it gives rise to topographical maps.

Answer 37

So the basic idea here is that the eye and the tectum express inverse gradients of receptors and signals (respectively) that allow these neurons to topographically map the eye on the brain

Question 38

Describe the importance of gradients in establishing the proper connections in the developing nervous system.

Answer 38

They’re hella important (too lazy to finish)