Chapter 4: Nervous System Development

Question 1

What causes different daughter cells to express different genes, given that all cells in the body contain the same DNA?

Answer 1

transcription factors: proteins that bind to DNA and promote or repress the expression of genes close to the binding site.

Question 2

5-6 days after fertilization, a human egg has divided to become a ____.

Answer 2

blastocyst

Question 3

At what stage in development would separation of embryonic stem cells result in an identical twin?

Answer 3

separation of cells in the blastocyst stage.

Question 4

the ells of the blastocyst rearrange themselves during ____ to form 3 distinct ___ layers:

Answer 4

during gastrulation to form 1) ectoderm

2) endoderm
3) mesoderm

Question 5

the ____derm layer differentiates into skin and _____ ___

Answer 5

the ECTODERM differentiates into skin and nervous system.

Question 6

Chordin is a ___ ___, that causes ectodermal cells to differentiate into ____ ____

Answer 6

Chordin is a neural inducer, that causes ectodermal cells to differentiate into NEURAL TISSUE

Question 7

How does chordin cause ectodermal cells to differentiate?

Answer 7

it inhibits bone morphogenetic protein, which is secreted by cells in the ventral portion of the embryo.

Question 8

bone morphogenetic protein is secreted in the ___ portion of the embryo. Any ectoderm cell that come in contact with this protein becomes ___. Where is BMP inhibited?

Answer 8

secreted in the ventral portion of the embryo. skin. But when BMP approaches the DORSAL BLASTOPORE LIP, chordin inhibits it from interacting with the ectoderm cells, making them become the nervous system.

Question 9

after BMP and chordin divided the ectoderm into neural and skin dorming portions, the emergind nervous system is called the ___ ___, which lifts up and becomes the ___ ____

Answer 9

after BMP and chordin divided the ectoderm into neural and skin dorming portions, the emergind nervous system is called the NEURAL PLATE, which lifts up and becomes the NEURAL GROOVE.

Question 10

How does the neural groove become the neural tube

Answer 10

neural groove cells express different adhesion molecules, which make them stick to one another but not to the skin cells.The overall effect of this selective adhesion is that the nrual groove comes a neural tube that is separate from and covered by the skin.

Question 11

the neural tube closes at the front and the rear and goes to form the __ and ___ ___

Answer 11

brain and spinal cord

Question 12

the neural ___ cells migrate away from the skin and neural plate and form the ___ nervous system. What else do they form? (non-nervous system)

Answer 12

the neuralCREST cells migrate away from the skin and neural plate and form the PERIPHERAL nervous system.

Also form skin melanocytes and skull.

Question 13

the spinal cord develops from the ___ portion of the neural tube, and the brain develops from the ___ end.

Answer 13

the spinal cord develops from the CAUDAL portion of the neural tube, and the brain develops from the ROSTRAL end.

Question 14

____ acid is a primary molecule that is responsible for caudalizing the neural tube to form the spinal cord from the caudal portion

Answer 14

retinoic acid

Question 15

what would happen if you interfered with retinoic acid signalling?

Answer 15

it would prevent caudal brain regions from forming normally.

Question 16

increasing retinoic acid levels to wayyy above normal would:

Answer 16

impair the differentiation of rostral brain regions and overaccentuate the development of the spinal cord ( caudal) region.

Question 17

rostrocaudal neural tube patterning involves ___ genes. What kind of genes are these? How are they activated?

Answer 17

Hox. transcription factor genes.

They are activated by different concentrations of retinoic acid. Different numbers of hox genes are activated dependening on how caudal the region is.

Question 18

the mesoderm gives rise to:

Answer 18

muscle, connective tissue and RBCs

Question 19

the endoderm gives rise to

Answer 19

digestive tract and lungs

Question 20

How are hox genes expressed?

Answer 20

how the NUMBER of different Hox genes expressed within a hindbrain segment INCREASES as you get to more CAUDAL segments of the HIND BRAIN

Question 21

a noteable protein involved in dorsoventral patterning in the SPINAL CORD is ___ ____.

Answer 21

Sonic Hedgehog SHH

Question 22

SHH is secreted by cells at the neural tube’s ___ midline, known as the __ ____

Answer 22

SHH is secreted by cells at the neural tube’s VENTRAL midline, known as the FLOOR PLATE

Question 23

SHH diffuses freely away from its floor plate source, forming a ___ to ___ concentration gradient wihtin the developing spinal cord

Answer 23

VENTRAL TO DORSAL CONCENTRATION GRADIENT.

Question 24

In addition to SHH ____ the spinal cord, SHH induces the cells to become ___ neurons

Answer 24

In addition to SHH VENTRAL the spinal cord, SHH induces the cells to become MOTOR neurons

Question 25

SHH exerts its ventralizing effects by turning on ___ ___

Answer 25

transcription factors (2 classes)

Question 26

two different transcription factor types that are affected by SHH, and what do they cause

Answer 26

1) induced transcription facts: activated at dif concentrations of SHH, causes DORSAL expression boundaries
2) repressed transcription factors: repressed at dif concentrations of SHH. causes VENTRAL expression boundaries.

Question 27

in general, the expression of domains of the SHH-induced genes and the SHH-repressed genes are ____

Answer 27

complementary. as one shh-induced gene fades out, an SHH-repressed gene expresion fades in, allowing the spinal cord to become divided into genetically distinct dorsoventral domains.

Question 28

Levels of retinoic acid ____ gradually as you go further caudally in the nervous system.

Answer 28

INCREASE. More retinoic acid in caudal region= more hox activation = more caudalization

Question 29

SHH acts as a ___ signal throughout the neural tube

Answer 29

VENTRALIZING, including both the brain and the spinal cord

Question 30

the midbrain-hindbrain boundary ___ center secretes transcription factors such as ___ ___ __ (FGF8). What is FGF8 crucial for?

Answer 30

the midbrain-hindbrain boundary SIGNALLING center secretes transcription factors such as FIBROBLAST GROWTH FACTOR 8 (FGF8).

FGF8 is crucial for proper midbrain and cerebellum development.

Question 31

the _____ signalling center secretes ____, like the ventral midline/floor plate. However, ___ does not act as a ventralizing signal, but instead helps to develop the pattern of the ___

Answer 31

the INTRATHALAMICsignalling center secretes SHH, like the ventralmidline/ floor plate. However, SHH does not act as a ventralizing signal, but instead helps to develop the pattern of the THALAMUS

Question 32

the anterior neural ridge secretes ____. What is its function?

Answer 32

FGF8, just like the midbrain-hindbrain boundary does. However, instead of cerebellum development, FGF8 in this case is responsible for rostrocaudal patterning in the brain.

Question 33

Lack of FGF8 expression in the rostral forebrain (lack of FGF8 from the ___ ___ ___ signalling cetner) causes structures ____ to develop in an abnormally ____ location.

Answer 33

Lack of FGF8 expression in the rostral forebrain (lack of FGF8 from the anterior neurla ridge singlaling center) causes structures (ex/ somatosensory cortex) to develop in an abnormally ROSTRAL location.

Question 34

an abnormally caudal source of fgf8 causes _____ of structures

Answer 34

duplication. Typically, FGF8 is secreted rostrally (anterior rostral ridge). Adding FGF8 caudally as well will generate a duplicate structurely, namely, 2 somatosensory cortices.

Question 35

T/F: patterning of the forevrain involves FGF8 and HOx genes, like the patterning of the hind brain and spinal cord.

Answer 35

FALSE. patterning of the forebrain needs FGF8 and SHH, but the spinal cord needs SHH and HOX genes. Forebrain patterning does not rely of Hox genes, which typically are responsible for driving the caudalization of the spinal cord.

Question 36

undifferentiated cells are called

Answer 36

progenitors

Question 37

young cells typically migrate ____

Answer 37

radially away from their place of birth

Question 38

during neurogenesis, progenitor cells in the walls of the young neural tube are called ___ ___ because they have a process that extends ___ away from the cell body toward the brain’s ____ surface.

Answer 38

during neurogenesis, progenitor cells in the walls of the young neural tube are called RADIAL CELLS because they have a process that extends RADIALLY away from the cell body toward the brain’s EXTERNAL surface.

Question 39

in neurogenesis, when the cell body is near the external brain surface, the progenitor cells ____, and when the cell body is near the boarder of the ventricle, the cell ____. After each cell division, the cell bodies of the two daughter cells move ___ away from the ___ surface and ___ the cycle.

Answer 39

in neurogenesis, when the cell body is near the external brain surface, the progenitor cells DUPLICATE THEIR DNA, and when the cell body is near the boarder of the ventricle, the cell DIVIDES BY MITOSIS.
After each cell division, the cell bodies of the two daughter cells move RADIALLY away from the VENTRICULAR surface and REPEAT the cycle.

At some point they stop dividing and then they differentiate into neurons (neurogenesis)

Question 40

early progenitors divide on the __ surface of the developing brain

Answer 40

ventricular

Question 41

role of beta catenin in neurogenesis

Answer 41

beta catenin is influenced by transcription factors and DELAYS neurogenesis. Delaying neurogenesis allows progenitor cells to keep dividing at the ventricular surface and migrating radially to the external surface over and over and over again without differentiating. When they finally differentiate, the brains are much larger than normal.

Question 42

role of delta-1 in neurogenesis.

Answer 42

progenitor cells leave the cell cycle early and begin neurogenesis without dividing/replicating as many times as they should’ve. May result in a smaller brain (because once the progenitor cell differentiates into neurons, they do not divide and replicate)

Question 43

newborn cells tend to migrate ___ away from the ___ zone and form a separate layer called the ____ zone that extends from the ___ zone to the ___ surface.

Answer 43

newborn cells tend to migrate RADIALLY away from the VENTRICULAR zone and form a separate layer called the MANTLE zone that extends from the VENTRICULAR zone to the EXTERNAL BRAIN surface. This zone continues to thicken as young cells migrate to the external brain surface.

Question 44

the mantle zone contains mainly ____ cells. Exceptions?

Answer 44

mainly contains post-proliferative cells.

Exception: in the telencephalon (cerebrum); they still contain progenitor cells that can divide at least one more time. They form the SUBVENTRICULAR ZONE.

Question 45

T/F different brain regions exhibit different patterns of radial neuronal migration

Answer 45

TRUE.
in neocortex; newer cells migrate past the older cells, where first born cells make up the deep cortical laters, and younger cells occupy progressively more superficial layers

in the retina; younger cells make up deeper layers (migrate less) than older cells, which migrate more radialyl away and occupy external layers.

Question 46

When do new migrating young neurons stop moving radially?

Answer 46

when they encounter a REELIN signal near the external surface.

Question 47

T/F: the time at which a cell is born affects not only its position in the adult brain but also the type of cell it will become.

Answer 47

True.

in the neocortex, younger cells make up more superficial layers while older cells make up regions near the ventricular zone.

cell type is also affected: neurons are made before glial cells, and oligodendrocytes are made before astrocytes.

Question 48

T/F new neurons migrate really far away from where they are born. Exceptions?

Answer 48

false. Usually they migrate radially but not far. tangential migration is exhibited in neurons that make a tract from the telencephalon to the dorsal thalamus in humans though.

Question 49

T/F axons grow from the young neuron as it migrates radially.

Answer 49

false axons grow out of the cell body once the neuron stopped migration.

Question 50

growing axons are filled with ___ and tipped with ___ ___>

Answer 50

growing axons are filled with MICROTUBULES and tipped with GROWTH CONES

Question 51

axon growth cones move forward by extending ____ made of ____ filaments

Answer 51

axon growth cones move forward by extending FILOPODIA made of ACTIN filaments

Question 52

Actin filaments of the filopodia are anchored to the ____ near the grwoth cone’s centers and to the __ ___ near the filopodia tips.

Answer 52

Actin filaments of the filopodia are anchored to the MICROTUBULES near the grwoth cone’s centers and to the CELL MEMBRANE near the filopodia tips.

Question 53

how are filapodia lengthened?

Answer 53

actin subunits are added to the actin filaments to extend the filopodia, pushing the filopodia forward.

Question 54

in order for filopodia to make the growth cone move, what must happen?

Answer 54

the filopodia tips must adhere to something in the external environment. ex/ must “pull” the axonal growth cone. The growth cone is pulled forward toward the filopodial tip. as the growth cone moves forward, the azon behind it elongates

Question 55

how does an axon grow in a specific direction?

Answer 55

the filopodia extend equally in all directions, but the direction in which the axon moves is dependent on

1) howw well the filopodia can stick to their surroundings o ‘pull” the growth cone, and
2) how likely the growth cone is to extend its filopodia in a particular direction.

Question 56

The ___ ___ is where young cortical neurons end their migration and begin to differentiate

Answer 56

CORTICAL PLATE (external layer of the brain)

Question 57

Explain how growth cones and thus axon directional grwoth exhibits characteristics of chemotaxis (2)

Answer 57

the growth cones can grow and move depending on concentration gradients of specific molecules, such as SEMAPHORIN PROTEINS.

1) The presence of semaphorin proteins repels growth cones from that region and causes filopodia to collapse, preventing the axon from extending to the region.
2) neurons exhibit JOURNEY SEGMENTATION/AXON REPROGRAMMING. Axons “reprogram” to what they are attracted/repelled by as they move throughout the brain region. It must stop being attracted to molecules secreted by the first target and start responding to new cues in novel ways.

Question 58

explain an example of axonal reprogramming

Answer 58

axons of commissural neurons in the spinal cord grow TOWARDS the floor plate, cross the midline, and then grow UP on the other side of the spinal cord. This is because the floor plate secretes NETRIN, which the growth cones have an affinity for because it acts on the DCC receptor. When the growth cones reach the grwoth plate, the axons make a receptor called ROBO, which makes it repulsed by SLIT and REPRESSES THE DCC, which is secreted by the growth plate as well.

Because the commissural spinal cord neuron is no longer attracted to netrin because of DCC receptor repression, and is now repulsed by slit because of ROBO, it moves away from the spinal cord and ascends on the contralateral side from where it grew on.

Question 59

Netrin is expressed at the ____ ____ of the brain and spinal cord

Answer 59

ventral midline/ FLOOR PLATE. It attracts commissural neurons

Question 60

What are the two proposed models for cortical lamination. What protein does it involve?

Answer 60

1) detach and stop
2) detach and go

both involve reelin protein that is secreted near the external surface (cortical plate)

Question 61

Neurons are derived from multipotent _____ cells that line the cerebral ventricles.

These ____ cells divide in the bentricles, and can turn into ___ ___ cells that either:

Answer 61

neuroepithelial

these neuroepithelial cells divide in the ventricles, and can either turn into RADIAL GLIAL cells that provide the scaffolding for neuronal migration or give rise to PRIMARY/PIONEER NEURONS which migrate to the cortical surface and provide a TRAIL for newer neurons to follow.

Question 62

the first phase of neurogenesis occurs in the ___ zone and generates ____ neaurson

Answer 62

ventricular zone and generates pioneer nerons.

Question 63

2 phases of neuronal proliferation

Answer 63

1) neurogenesis of prioneer neurons in the ventricular zone from neuralepithelial cells
2) neurogenesis of projection neurosn in the subventricular zone.

Question 64

radial glia serve a dual purpose as ___ ___ and as ___ for locomotion of the neuronal precursors.

Answer 64

radial glia (made from neuroepithelial multipotent tissue) are both PROGENITOR CELLS (migrate up, duplicate Dna, migrate down to ventricle, divide), and as GUIDES for locomotion.

Question 65

___ was found to induce ___ of neurons from radial glia. Thisprotein is highly expressed in the ____ zone, where neurons stop moving

Answer 65

REELIN was found to induce DETACHMENT of neurons from radial glia. This protein is highly expressed in the MARGINAL/ MANTLE zone, where neurons stop moving

Question 66

Explain the detach and go model

Answer 66

Recall: radial glia made in the ventricular level of the brain extend projections that provide guidance to migrating young neurons.

Early in development of the normal cortex, future layer VI neurons have an ascending process that reaches the marginal zone. Reelin stimulates these cells to translocate through the subplate.
Later in development, future layer V and subsequent cells initially use locomotion to ascend radial glia. However, when the leading process enters the marginal zone, the cell body detaches from the radial glia, and Reelin stimulates somal translocation to BRING THE CELL BODY PAST OLDER CELLS

Therefore, after reelin promotes the detachment of neuron cells from the radial glia, the new cells continue to migrate upwards to more external surfaces.

Question 67

The chemoaffinity hypothesis for the development of the reinotectal system

Answer 67

each retinal exon ecpresses a distinct set of molecular markers, anad the textal neurons express matching markers. AS the retinal axons grow into the textum during embryonic development, they seek out and selectively terminate with the matching marker in the textum.

This allows for the HIGHLY TOPOGRAPHIC ORGANIZATION of the retinotectal system, where Nasal retina projects to caudal tectum, temporal retina to rostral tectum, dorsal retina to lateral tectum, and ventral retina to medial tectum.

TECTUM=SUPERIOR COLLICULUS IN MAMMALS

Question 68

What type of protein helps guide ___ axons?

Answer 68

EPHRIN. Its levels increase towards the caudal edge of the tectum, preventing TEMPORAL RETINA AXON GROWTH.

Question 69

Explain the ephrin gradient in the tectum/superior colliculus. How does this affect the distribution of nasal and temporal retina axonal growth?

Answer 69

ephrin levels are higher in the caudal edge of the tectum. Nasal retinal axons do not have many ephrin receptors and thus are NOT AS RESPONSIVE to ephrin, allowing them to grow into the caudal region of the tectum.

Temporal axons contain more ephrin receptors and are thus more sensitive to eprhin.they are REPELLED by high levels of ephrin and thus do not grow towards the caudal region of the tectum as heavily.

Question 70

how do dendrites grow?

Answer 70

in the same manner as axons. dendrites also exhibit filopodia that extend via addition of actin filaments. Dendritic filopodia either retract after forming, or develop into new dendritic branches.

Question 71

What is dendritic tiling?

Answer 71

process in which dendrites grow with very little overlap. They tend to be repulsed by dendrites of the same type.

Question 72

Why is dendritic tiling so important?

Answer 72

allows for dendritic branching of a single neuron to spread far and wide rather than being clumped. this spreading is importnat for pukinje cells of the cerebellum because it MAXIMIZES the ability to gather inputs from many different axons.

Question 73

2 overall processes of synapse formation

Answer 73

1) pre and post synaptic elements are found to be compatible (ex/ axon terminal contains GABA, and the post syn dendrite has GABA receptors
2) adhesion moelcules ensure that budding synapses do not get pulled apart

Question 74

role of agrin in synapse formation

Answer 74

forms synapses between muscle and motor neuron.

agrin gets released from motor neuron and causes acetylcholine receptors in the muscle membrane to cluster right beneath the axon’s contact point.

Question 75

role of neurexin in synapse formation

Answer 75

resides in the presynaptic membrane and binds to receptors in the post syn cell. Activation of the neurexin receptor then induces the post ysn side of the synapse to accumulate various scaffolding proteins and neutransmitter receptors, which together form the post synaptic density.

Question 76

Outline the bidirectional interactions during synapse formation

Answer 76

2) axonal filopodium first makes contact with dendritic filopodium
2) special cell adhestion molecules stick the filopodia together
3) of bidirectional molecular interactions that cause synaptic vesicles and various proteins needed for transmitter release to accumulate on the axonal side of the emerging synapse; postsynaptic proteins accumulate on the dendritic side. Many of the synaptic molecules are “prepackaged” into macromolecular assemblages that float around axons and dendrites and can be inserted rapidly into emerging synapses.
4) SYNAPSE MATURATION: young synapses become larger and accumulate a greater variet of pre and post synaptic proteins. Strength of synaptic transmission increases.

Question 77

Neuron death is partially regulated by ___ __

Answer 77

target size. less leg tissue= fewer leg motor neurons. More leg tissue = more leg motor and sensory neurons.

Question 78

example for numerical matching hypothesis

Answer 78

granule cells must synapse with purkinje cells in order to remain alive.

Although purkinje cells receive inputs from different cells, granule cells only synapse with purkinje cells. if they do not synapse, they commit apoptotic suicide.

This is shown by the fact that granule cells and purkinje fibers exist in a 1;1 ratio.

Question 79

Trophic factors, such as ___ ___ ___ is a molecule that promotes neuron survival and works against cell death

Answer 79

NERVE GROWTH FACTOR.

Question 80

two types of “signalling” of trophic factors that allow for numerical matching.

Answer 80

1) retrograde signalling: trophic factors are transported from a neuron’s terminals back to the cell body.
2) anterograde signalling: trophic factors originate from a neuron’s inputs rather than its targets.

Question 81

Explain an example how neural activity regulates pruning of axons.

Answer 81

can be seen in the pruning of retinogeniculate axons.

Blocking retinal waves in just one retina (C) causes the more active retina to end up with a proportionately larger projection to the LGN.

Lack of activity results in too much PRUNING and destruction of the “unused” retinal pathway, and the additional development of the “used” pathway.

Sort of Hebbian.

Seen in modification of ocular dominance columns:

The bands corresponding to the OPEN/ACTIVE left eye have expanded relative to the bands corresponding to the closed eye. these findings indicate that visual activity in both eyes is required to maintain the normal pattern of ocular dominance bands.

Question 82

___ waves and ___ palsticity can refine topographic projections

Answer 82

ACTIVITY waves and HEBBIAN PLASTICITY.

A matching wave spreads across the target neurons, which fire only if they receive simultaneous input from at least two input neurons.
According to Hebb’s rule, synapses that contributed to firing a target cell are strengthened; all others are weakened.