Neurogenesis Connectivity and Cell Death

Question 1

In the neuronal proliferation, what surface do ventricular zone cells extend a process towards?

Answer 1

The pial surface

Question 2

What happens to the neuronal nuclei as they move towards the pial surface in neuronal proliferation?

Answer 2

The DNA is copied

Question 3

What are steps 3 and 4 of the cell proliferation/cleavage process?

Answer 3

3. The cells move back to the ventricular surface
4. Cell retracts arm from pial surface

Question 4

What are the two types of neuron cleavage?

Answer 4

Horizontal division (vertical cleavage)

Vertical division (horizontal cleavage)

Question 5

What other classifications of division comes from the different cleavage types?

Answer 5

Vertical cleavage = symmetric division
Horizontal cleavage = Asymmetric division (differentiation)

Question 6

What type of cleavage would be responsible for rapid growth of neuronal cell population?

Answer 6

Vertical cleavage/horizontal division

Question 7

How does a cell decide on the type of cleavage?

Answer 7

The transcription factor

Question 8

What is the notch and numb?

Answer 8

They are the differing transcription factors on the top/bottom of a proliferating neuronal stem cell

Question 9

How can we describe the daughter cells of horizontal and vertical division in terms of notch/numb?

Answer 9

Vertical cleavage/ horizontal division = both cells contain notch/numb

Horizontal cleavage/vertical division = one cell contains notch(differentiates) and the other contains numb (will eventually develop notch again)

Question 10

What are the two transcriptions factors that determine the fate of the daughter cells and on which sides of the cell are they located?

Answer 10

Notch one = pial-facing surface
Numb = ventricular surface

Question 11

In terms of notch and numb, when will a cell stop its division?

Answer 11

Notch by itself will stop dividing

Question 12

What is the mechanism of microcephaly genes?

Answer 12

They tilt the mitotic spindle more horizontally, meaning more vertical division, meaning less premitotic cells

Question 13

What kinds of division lead to exponential vs linear growth?

Answer 13

Horizontal division = exponential growth
Vertical division = linear growth

Question 14

What are the 5 zones of the cortex in terms of neuronal development?

Answer 14

Marginal zone
Cortical plate
Intermediate zone
Subventricular zone
Ventricular zone

Question 15

What kinds of cells are found in the ventricular zone?

Answer 15

Radial glial cells

Question 16

What is the order of cortical plate development and neuronal layers in the cortex?

Answer 16

Earliest to latest:
Cortical subplate (eventually disappears)
Cortical Plate (eventually disappears)
Layer 6
Layer 5
-
-
Layer 1

Question 17

What is the outer layer of the cortex?

Answer 17

Layer 1

Question 18

What are the factors that determine the fate of a differentiating cell?

Answer 18

1. Cleavage plane
2. The location of the cell in the ventricular zone
3. Migration pattern
4. Age of cell at time of division

Question 19

Name the types of cells differentiated by location of origin in ventricle wall from the most ventral to the most dorsal

Answer 19

Oligodendrocyte
GABAergic interneurons
Pyramidal neurons/cortical astrocytes

Question 20

What can we say about the nature of neuronal cell migration in the developing neocortex?

Answer 20

Ventral cells can migrate dorsally, and the dorsal cells are in the proliferative zone and are already situated in the right spot

Question 21

From ventral to dorsal, name the types of NTergic progenitor zones generated in the ventricular wall

Answer 21

AcH, GABA, Glu

Question 22

What are the excitatory/inhibitory properties of the NTs generated in the ventricular wall?

Answer 22

Glu and Ach = excitatory
GABA = inhibitory

Question 23

How can we describe the geometrical migration of GABAergic and Glutamatergic neurons

Answer 23

GABAergic migrates tangentially

Glutamatergic migrates radially

Question 24

Where do GABAergic and glutamatergic neurons originate?

Answer 24

GABAergic = lateral and media ganglionic eminences

Glutamatergic = pallium/ cortical ventricular zone

Question 25

What are the three stages of the development of glial cells in mice and around how many days into pregnancy does this occur?

Answer 25

1. Expansion phase (symmetric division) 8 days 2. Neurogenesis (asymmetric division)13 days 3. Gliogenesis (asymmetric division) 18 days

Question 26

What is gliogenesis?

Answer 26

The creation of glial cells from stem cells arise from progenitor cells

Question 27

What molecule is an example of diffusible molecules responsible for the direction and characteristics of neurons/ dendrites in the marginal zone?

Answer 27

Semaphorin 3A

Question 28

What is spatiotemporal pattern of gene expression?

Answer 28

it is a reference to the fact that cells differentiate at different places at different times and this affects their outcome

Question 29

What two transcription factors are relevant to the specification and regionalization of mice cerebral corticies?

Answer 29

Emx2 and Pax 6

Question 30

What areas of the brain were impacted by deficiencies in transcription factors?

Answer 30

Deficiency in Emx2 led to smaller visual cortex (larger motor to compensate) and a deficiency in pax6 led to a smaller motor cortex/ somatosensory cortex (larger visual cortex to compensate)

Question 31

What are the three phases of pathway formation?

Answer 31

1. Pathway 2. Target 3. Address

Question 32

What is the necessary environmental component for the extension of neurons, and what molecules are attached to this that are important?

Answer 32

The extracellular matrix allows for the growth of neurons because they hold the laminin molecules

Question 33

Why are laminin molecules important for axon growth?

Answer 33

They bind to the integrin molecules of the axon to direct the growth

Question 34

What parts of the growth cone search for clues in the ECM?

Answer 34

Filopodia and lamellipodia

Question 35

What is the role of a microtubule in the growth cone?

Answer 35

They are constantly assembled down the axon and are responsible for cell shape

Question 36

What are the roles of actin molecules in the growth cone?

Answer 36

They are the growing part of the cone and interact with myosin motor proteins to grow before the microtubules take their place and are eventually left behind

Question 37

What is the role of a CAS?

Answer 37

A cell adhesion molecule holds axons together, as they typically grow together and move as a group

Question 38

What is the main challenge in wiring the brain?

Answer 38

The distances between connected structures

Question 39

What is the role of a pioneer axon?

Answer 39

It stretches as the nervous system expands, it then guides the growth of neighboring axons (connecting dots)

Question 40

What is a pioneer tract?

Answer 40

It is the first group of axons to grow and find targets, they form a trail for other axons to follow.

Question 41

What are the two molecularly provided guidance clues to neuronal growth?

Answer 41

Chemoattraction and chemorepulsion

Question 42

What is the target area of growth for a pioneer tract called?

Answer 42

The target trophic support

Question 43

What causes the decussation of neurons in terms of guidance clues when there is a high concentration of chemoattractants and chemorepellents in the midline?

Answer 43

When the axons are on the initial side, they express receptors to the chemoattractants, and after they grow across the midline, they express the chemorepellent receptor and grow away form the midline

Question 44

How did the conclusion come about that growing axons have chemical markers that are matched by complementary chemical markers?

Answer 44

There are too many neurons to individually code the pathfinding for each neuron

Question 45

How did Roger Sperry study the topographic axon map of eyes?

Answer 45

He cut and rotated frog eyes, and they saw the world upside down

Question 46

What information did the frog eye experiment give us?

Answer 46

Optic nerves from the retina connected to the same place in the tectum

Question 47

What is the role of ephrin in the growth of retinal nerves?

Answer 47

Ephrin A2 and A5 are responsible for the topographic arrangement of retinal cone growth. Retinal cones have ephrin A3 receptors. When ephrin A2 was applied globally, nerves died indicating that ephrin A2 is a growth repellant.

Question 48

What parts of the tectum do the retinal tracts attach to?

Answer 48

Temporal retina attach to anterior tectum Nasal retina attach to posterior tectum (or both)

Question 49

What are the three steps to CNS synapse formation?

Answer 49

1. Filipodium contacts axon 2. Synaptic vesicles and active zone proteins are recruited to the presynaptic membrane 3. Receptors accumulate on postsynaptic membrane

Question 50

What is the difference between necrosis and apoptosis?

Answer 50

Necrosis is accidental cell death (swelling/rupture) and apoptosis is programmed cell death (shrinkage/fragmentation)

Question 51

At what age does neural pruning in the embryo end?

Answer 51

25 weeks

Question 52

What determines neuronal survival?

Answer 52

Competition (for trophic factors)

Question 53

What are the types of trophic factors + mechanisms?

Answer 53

Endocrine - from the blood/circulation Paracrine - from other cells autocrine/juxtracrine - from the cell itself