embryo 2

Question 1

Know when and where neurogenesis occurs.

Answer 1

neurectoderm (single layers) becomes neural tube, and proliferation of cells occurs in ventricular zones (layer closest to neural tube lumen). Neurogenesis occurs prior to birth for most CNS regions, except cerebellar granule neurons, olfactory and hippocampal neurons which are born postnatally

Question 2

Describe the changes in nuclear position that occur during the cell cycle of neuronal precursors.

Answer 2

Interkinetic nuclear migration: Cell processes attach to ventricular surface (medially) and to the external surface (laterally) during all phases but mitosis. S phase: nuclei most superficial. M phase: nuclei are most deep. Gap phases (G1, 2): nuclei are intermediate to S and M phases

Question 3

Describe methods used to study neurogenesis.

Answer 3

Involve labeling dividing cells with detectable DNA precursors (e.g., 3H-thymidine or bromodeoxyuridine). Cells take up the precursors during S phase. The incorporated label allows the cells and their progeny to be tracked

Question 4

Know what is meant by a neuron’s birthdate. Does a neuron’s birthdate influence its differentiation?

Answer 4

A cell’s birthdate is defined as the time it undergoes its last round of DNA synthesis (S phase). After a cell’s birthdate, it divides and makes the decision to exit the cell cycle from M phase. It detaches its process from ventricular surface and differentiation can now begin

Question 5

Know which brain regions are areas of secondary neurogenesis.

Answer 5

Secondary zones of neurogenesis are specific regions of the brain that are hot spots of postnatal neurogenesis. Includes External granule layer of cerebellum, subventricular zone (olfactory neurons), dentate gyrus (hippocampal neurons),

Question 6

Describe development in external granule layer and when it occurs

Answer 6

cells from 4th ventricle migrate here before becoming postmitotic. Granule cell progenitors proliferate in the external granule layer and when they exit the cell cycle, they migrate into the cerebellum. Cerebellar granule cell neurogenesis
can persist up to postnatal year two in humans.cells from 4th ventricle migrate here before becoming postmitotic. Granule cell progenitors proliferate in the external granule layer and when they exit the cell cycle, they migrate into the cerebellum. Cerebellar granule cell neurogenesis
can persist up to postnatal year two in humans.cells from 4th ventricle migrate here before becoming postmitotic. Granule cell progenitors proliferate in the external granule layer and when they exit the cell cycle, they migrate into the cerebellum. Cerebellar granule cell neurogenesis
can persist up to postnatal year two in humans.cells from 4th ventricle migrate here before becoming postmitotic. Granule cell progenitors proliferate in the external granule layer and when they exit the cell cycle, they migrate into the cerebellum. Cerebellar granule cell neurogenesis
can persist up to postnatal year two in humans.

Question 7

Describe development in subventricular zone

Answer 7

Cells are initially located in a ventricular zone found in the anterior lateral wall of the lateral ventricles. They migrate just adjacent to where they were before into the subventricular zone. Subventricular zone cells exit mitotic cycle and become olfactory bulb neurons, then migrate rostrally to the olfactory bulb.

Question 8

3 characteristics of secondary zones of neurogenesis

Answer 8

(1) arise in a ventricular zone and (2) migrate, before exiting the mitotic cycle, to a new
non-ventricular location, and (3) proliferate postnatally in non-ventricular zone locations.(1) arise in a ventricular zone and (2) migrate, before exiting the mitotic cycle, to a new
non-ventricular location, and (3) proliferate postnatally in non-ventricular zone locations.(1) arise in a ventricular zone and (2) migrate, before exiting the mitotic cycle, to a new
non-ventricular location, and (3) proliferate postnatally in non-ventricular zone locations.(1) arise in a ventricular zone and (2) migrate, before exiting the mitotic cycle, to a new
non-ventricular location, and (3) proliferate postnatally in non-ventricular zone locations.

Question 9

Describe what is known about neurogenesis in the adult brain. What are key questions for future research?

Answer 9

neurogenesis occurs in the adult dentate gyrus and the subventricular zone giving rise to new neurons
in the hippocampus and olfactory bulb. Cell death also occurs, though, so total number of neurons stays the same. Death is highest in neurons generated during adulthood, well after birth and perinatal period. neurogenesis occurs in the adult dentate gyrus and the subventricular zone giving rise to new neurons
in the hippocampus and olfactory bulb. Cell death also occurs, though, so total number of neurons stays the same. Death is highest in neurons generated during adulthood, well after birth and perinatal period. neurogenesis occurs in the adult dentate gyrus and the subventricular zone giving rise to new neurons
in the hippocampus and olfactory bulb. Cell death also occurs, though, so total number of neurons stays the same. Death is highest in neurons generated during adulthood, well after birth and perinatal period. neurogenesis occurs in the adult dentate gyrus and the subventricular zone giving rise to new neurons
in the hippocampus and olfactory bulb. Cell death also occurs, though, so total number of neurons stays the same. Death is highest in neurons generated during adulthood, well after birth and perinatal period.

Question 10

Draw and describe an asymmetric/ symmetric cell division.

Answer 10

Symmetric division: When the plane of cleavage is
perpendicular to the ventricular surface, both daughter cells remain attached to the
ventricular surface. Asymmetric: Plane of cleavage is parallel to ventricular surface, so one of daughters remains attached to ventricular surface but the other does not.Symmetric division: When the plane of cleavage is
perpendicular to the ventricular surface, both daughter cells remain attached to the
ventricular surface. Asymmetric: Plane of cleavage is parallel to ventricular surface, so one of daughters remains attached to ventricular surface but the other does not.Symmetric division: When the plane of cleavage is
perpendicular to the ventricular surface, both daughter cells remain attached to the
ventricular surface. Asymmetric: Plane of cleavage is parallel to ventricular surface, so one of daughters remains attached to ventricular surface but the other does not.Symmetric division: When the plane of cleavage is
perpendicular to the ventricular surface, both daughter cells remain attached to the
ventricular surface. Asymmetric: Plane of cleavage is parallel to ventricular surface, so one of daughters remains attached to ventricular surface but the other does not.

Question 11

Know factors/mechanisms that determine when a cell stops dividing and begins differentiating.

Answer 11

During symmetric division, both daughters remain in cell cycle. During asymmetric division, the daughter that does not attach to ventricular surface usually contains proteins/mRNA that are not present in the attached daughter, and promote differentiation. Prospero, numb and miranda are genes that encode for the asymmetrically localized factors.

Question 12

For the cerebral cortex, know where the first-born cells are found with respect to the ventricular zone. What about the retina?

Answer 12

Neurons migrate from inside out in the cortex, so the first born neurons are closest to ventricular surface and later born are closest to outer pial surface. Neurons migrate from outside in in retina (ganglion cells born first, photoreceptors last

Question 13

Define preplate and subplate with respect to neuronal migration.

Answer 13

In the cerebral cortex, the first neurons to become postmitotic migrate away from the ventricular zone a distance of several cell bodies and form a new region known as the preplate (at 8-9 weeks). Preplate divides into marginal zone, cortical plate, intermediate zone (contains radial glia processes), subplate and deep ventricular zone (from pial surface to ventricular zone)

Question 14

What do neurons in the Marginal zone and cortical plate become

Answer 14

6 layers of cerebral cortex

Question 15

What does the intermediate zone become

Answer 15

white matter of brain

Question 16

Functions of subplate neurons

Answer 16

Neurons in the subplate region are among the earliest born and play “pioneering” roles
in circuit formation. Many of the subplate neurons die early once their roles have been played out, so are often considered a transient neuronal populationNeurons in the subplate region are among the earliest born and play “pioneering” roles
in circuit formation. Many of the subplate neurons die early once their roles have been played out, so are often considered a transient neuronal populationNeurons in the subplate region are among the earliest born and play “pioneering” roles
in circuit formation. Many of the subplate neurons die early once their roles have been played out, so are often considered a transient neuronal populationNeurons in the subplate region are among the earliest born and play “pioneering” roles
in circuit formation. Many of the subplate neurons die early once their roles have been played out, so are often considered a transient neuronal population

Question 17

Describe the role that radial glia play in neuronal migration.

Answer 17

Radial glia extend from ventricle to surface of cerebral cortex. After preplate formation, neurons use them as guides during migration.

Question 18

List 3 stages of neuronal migration in the cerebral cortex.

Answer 18

1- onset of migration, 2- ongoing migration, 3–migration stop

Question 19

Know genes that play a role in onset of neuronal migration in cerebral cortex and Conditions related to abnormal function

Answer 19

FilaminA (FLNA) encodes an actin-binding crosslinking protein involved in onset of migration. Periventricular heterotopia (PH) is a condition where FLNA is mutated and neurons haave problems leaving ventricular zone, so adults have differentiated neurons in the ventricular zone forming nodules. PH is x-linked dominant. Males dont survive to term and females have epilepsy and cognitive problems

Question 20

Know genes that play a role in neuronal migration in cerebral cortex and Conditions related to abnormal function

Answer 20

LISI regulates microtubular cytkoskeleton function associated with nuclear movement. A single mutation of LISI results in type 1 lissencephaly (smooth brain) where neurons exit ventricular zone, do not make it to the cortical plate. mental retardation and epilepsy. Doublecortin (DCX) on X chromosome regulates microtubule polymerization and when mutated produces lissencephaly like symptoms in males and double cortex syndrome in females (mental disability, epilepsy and subcortical band heterotopia)

Question 21

Know genes that play a role in stopping neuronal migration in cerebral cortex

Answer 21

Reeler is expressed by Cajal-Retzius neurons in preplate and plays a role in decision to stop migrating. Reeler mutations cause inversion of the inside out pattern, and cerebellar problems. Vldlr and Apoer2 protein products function as reelin receptors on neurons in the cerebellum and cerebral cortex, respectively. Dab1 codes for an intracellular protein, that plays a role in the intracellular transduction of the reelin signal

Question 22

Define radial, tangential and chain migration.

Answer 22

Radial: neurons in cortex travel from inside to outside via radial glia, and progeny are found in clusters. Tangential: progeny are dispersed throughout a tissue and don’t use radial glial cells. Chain: Also does not involve radial glial cells, rather neuronal precursors move as chains in the rostral migratory stream

Question 23

What class of neurons undergoes radial migration?

Answer 23

glutamate-containing neurons (pyramidal cells)

Question 24

What is radial migration important for

Answer 24

layer formation, column formation and coordination of neurogenesis

Question 25

What class of neurons undergoes tangential migration?

Answer 25

inhibitory GABA-containing neurons

Question 26

What class of neurons undergoes chain migration?

Answer 26

Olfactory bulb neurons from subventricular zone

Question 27

Once a developing neuron migrates to its final position, what does it do

Answer 27

It usually interacts with other developing neurons via surface membrane proteins to form a distinct nucleus or layer.

Question 28

Know what neural crest cells are. What neuronal populations do they give rise to?

Answer 28

Neural crest is a mass of cells on top of the dorsal side of the neural tube, and the neural crest cells give rise to the peripheral nervous system, pigment cells and cartilage. They are found in the gut, skin and sensory ganglia.

Question 29

Contrast migration of neural crest cells to radial migration in the cerebral cortex.

Answer 29

Neural crest cells don’t use guides like radial glia. The crest cells position along rostro-caudal axis prior to migration influences its fate. Two paths: 1. The dorsal (lateral) stream flows dorsolaterally underneath the ectoderm but lateral to the myotomes and gives rise to pigment cells. 2. The ventral stream flows ventromedially, dives under dorsal dermamyotomes (DM) and gives rise to the peripheral NS (sensory, autonomic and enteric ganglia).

Question 30

Molecules involved in neural crest migration

Answer 30

Laminin and fibronectin are proteins in ECM that bind to integrins on neural crest cells. Laminin and fibronectin are permissive factors, while other molecules serve as non permissive factors. Neural crest cells will migrate through areas with permissive substrates, but do not migrate through areas of non permissive substrates.

Question 31

Compare and contrast “apoptosis” with “necrosis”.

Answer 31

Necrosis occurs in response to extreme changes in
physiological conditions and leads to death of cells by loss of membrane integrity; neighboring cells are often exposed to the contents of the dying cell. Mitochondria and the endoplasmic reticulum swell. Necrotic cell death is associated with trauma and
other forms of external injury. In contrast, apoptosis occurs under normal physiological conditions and the cell actively participates in its own demise. Apoptosis leads to removal of cells by phagocytosis; neighboring cells are shielded from the intracellular contents of the dying cell.Necrosis occurs in response to extreme changes in
physiological conditions and leads to death of cells by loss of membrane integrity; neighboring cells are often exposed to the contents of the dying cell. Mitochondria and the endoplasmic reticulum swell. Necrotic cell death is associated with trauma and
other forms of external injury. In contrast, apoptosis occurs under normal physiological conditions and the cell actively participates in its own demise. Apoptosis leads to removal of cells by phagocytosis; neighboring cells are shielded from the intracellular contents of the dying cell.Necrosis occurs in response to extreme changes in
physiological conditions and leads to death of cells by loss of membrane integrity; neighboring cells are often exposed to the contents of the dying cell. Mitochondria and the endoplasmic reticulum swell. Necrotic cell death is associated with trauma and
other forms of external injury. In contrast, apoptosis occurs under normal physiological conditions and the cell actively participates in its own demise. Apoptosis leads to removal of cells by phagocytosis; neighboring cells are shielded from the intracellular contents of the dying cell.

Question 32

Know when cell death occurs in the nervous system.

Answer 32

At roughly the same time as when that neuron population is establishing connections. Trophic factors from target organs, pre-synaptic cells and non-neuronal cells (glia) play a role (deprivation of these factors leads to apoptosis)

Question 33

Define and describe what are neurotrophins. What roles do they play in neuronal development?

Answer 33

Neurotrophins promote cell survival. Nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrphin-3 (NT-3), NT-4/5 and CNTF are examples. Each neurotrophin can activate one or more tropomyosin-related kinase membrane receptors (Trk), which leads to Trk dimerization and recruitment of intracellular signaling molecules

Question 34

pair neurotrophins with their most common Trk receptor

Answer 34

NGF: TrkA. BDNF and NT-4/5: TrkB. NT-3: TrkC

Question 35

What role do neurotrophins play in axon development

Answer 35

It is thought that neurotrophins play an early
“permissive” role in axon outgrowth. With respect to axons, the primary function of neurotrophins is to allow cells to extend processes rather than guide them to targets (pathfinding).It is thought that neurotrophins play an early
“permissive” role in axon outgrowth. With respect to axons, the primary function of neurotrophins is to allow cells to extend processes rather than guide them to targets (pathfinding).

Question 36

growth cone

Answer 36

growing tip of the axon where membrane, cytoskeletal proteins and other components are added. The growth cone continuously extends and retracts fine processes (filopodia) that “sniff” the biochemical environment and regulate growth of the axon.

Question 37

long range vs short range axon guidance molecules

Answer 37

Long range: diffusible. Short range: bound to cell membranes or extracellular matrices, require direct cell contact to exert effect.

Question 38

Provide examples of long-range axon guidance molecules.

Answer 38

netrins (attractive and repulsive), semaphorins (repulsive)

Question 39

Provide examples of short-range axon guidance molecules.

Answer 39

Attractive: cadherins and CAMs (cell surface), collagen, laminin, fibronectin and proteoglycans (ECM). Repulsive: semaphorins and ephrins (cell surface), tenascin (ECM)

Question 40

specific roles of CAMS

Answer 40

outgrowth, adhesion and fasciculation of axons

Question 41

Know factors that influence the ability of axons to regenerate.

Answer 41

the ability of axons to grow, the presence of molecules that promote growth and the presence of molecules and receptors that inhibit growth

Question 42

Are CNS axons alone capable of regenerating long distances

Answer 42

yes. If a peripheral nerve is implanted at the site of injury in the cord, the CNS axons can grow many
centimeters in the peripheral nerve.yes. If a peripheral nerve is implanted at the site of injury in the cord, the CNS axons can grow many
centimeters in the peripheral nerve.

Question 43

Which molecules promote axonal regeneration

Answer 43

neurotrophin ,FGF

Question 44

Which molecules inhibit axonal regeneration

Answer 44

CNS myelin expresses Nogo which prevents axonal regeneration.

Question 45

Do axons regenerate in the CNS

Answer 45

usually not

Question 46

Define synapse elimination.

Answer 46

Selective synapse elimination is the competitive process of reducing the number of cells contacted by a single neuron. Ie. In early neonate, single muscle fiber recieves input from several motor neurons, but as adult each muscle fiber is contacted by only one neuron (although that single motor neuron will increase the its number of synapses, so the total number of synapses may not decreases)

Question 47

When and where does synapse elimination occur?

Answer 47

In motor neurons, postnatally (about 4th week postnatal). Also in CNS, purkinje cells are first innervated by many climbing fibers, but in an adult only by one climbing fiber. Electrical correlation of pre and post synaptic firing favors selective synapse stabilization

Question 48

Which neurotrophin is involved in epilepsy

Answer 48

BDNF increases in hippocampi of people with temporal lobe epilepsy.

Question 49

Describe normal postnatal changes in brain morphology?

Answer 49

At birth, the density of neural connections is low
compared to what is present at the end of childhood. During the first postnatal year, there are dramatic morphological changes in size of the soma and interconnections between neurons. The number of dendrites increases a lot, even when normalized to neuron number.

Question 50

How do Autism Spectrum Disorder and Down’s syndrome affect these normal developmental changes in neuronal morphology?

Answer 50

Autism: normal-small brain at birth with abnormally high increase in size during first postnatal year, especially in white matter. neuronal cell bodies are often smaller and dendrites branch less (abnormal pruning or synase maturation). Down’s: dendritic spines are abnormally thin and short

Question 51

Know when myelination occurs.

Answer 51

Begins during embryonic stages, first in periphery. In CNS, observed first in spinal cord near the end of first trimester. Present in brain by third trimester. Several cortical tracts involved in higher functions occurs after birth, corticospinal tract begins before birth but only extends to regions more caudal than medulla after birth.

Question 52

Describe two ways in which function of GABA receptors is developmentally regulated.

Answer 52

In adult, E for Cl is near/negative to resting potential. During development, intracellular Cl is elevated resulting in a more depolarized value for E cl (so activation of GABA receptors leads to depolarization and excitation). Also, GABA receptors during development contain different isoforms than during adult stages.

Question 53

Describe how nicotinic receptor changes during development

Answer 53

two a, beta, gamma, epsilon. The subunit composition embryonically is different from the adult

Question 54

functions of neurotrophins

Answer 54

survival, synapse elimination, synapse plasticity