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Flashcards in embryo 2 Deck (54):
1

Know when and where neurogenesis occurs.

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

2

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

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

3

Describe methods used to study neurogenesis.

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

4

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

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

5

Know which brain regions are areas of secondary neurogenesis.

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),

6

Describe development in external granule layer and when it occurs

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.

7

Describe development in subventricular zone

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.

8

3 characteristics of secondary zones of neurogenesis

(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.

9

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

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.

10

Draw and describe an asymmetric/ symmetric cell division.

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.

11

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

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.

12

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

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

13

Define preplate and subplate with respect to neuronal migration.

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)

14

What do neurons in the Marginal zone and cortical plate become

6 layers of cerebral cortex

15

What does the intermediate zone become

white matter of brain

16

Functions of subplate neurons

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

17

Describe the role that radial glia play in neuronal migration.

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

18

List 3 stages of neuronal migration in the cerebral cortex.

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

19

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

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

20

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

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)

21

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

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

22

Define radial, tangential and chain migration.

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

23

What class of neurons undergoes radial migration?

glutamate-containing neurons (pyramidal cells)

24

What is radial migration important for

layer formation, column formation and coordination of neurogenesis

25

What class of neurons undergoes tangential migration?

inhibitory GABA-containing neurons

26

What class of neurons undergoes chain migration?

Olfactory bulb neurons from subventricular zone

27

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

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

28

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

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.

29

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

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).

30

Molecules involved in neural crest migration

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.

31

Compare and contrast “apoptosis” with “necrosis”.

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.

32

Know when cell death occurs in the nervous system.

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)

33

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

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

34

pair neurotrophins with their most common Trk receptor

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

35

What role do neurotrophins play in axon development

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).

36

growth cone

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.

37

long range vs short range axon guidance molecules

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

38

Provide examples of long-range axon guidance molecules.

netrins (attractive and repulsive), semaphorins (repulsive)

39

Provide examples of short-range axon guidance molecules.

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

40

specific roles of CAMS

outgrowth, adhesion and fasciculation of axons

41

Know factors that influence the ability of axons to regenerate.

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

42

Are CNS axons alone capable of regenerating long distances

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.

43

Which molecules promote axonal regeneration

neurotrophin ,FGF

44

Which molecules inhibit axonal regeneration

CNS myelin expresses Nogo which prevents axonal regeneration.

45

Do axons regenerate in the CNS

usually not

46

Define synapse elimination.

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)

47

When and where does synapse elimination occur?

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

48

Which neurotrophin is involved in epilepsy

BDNF increases in hippocampi of people with temporal lobe epilepsy.

49

Describe normal postnatal changes in brain morphology?

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.

50

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

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

51

Know when myelination occurs.

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.

52

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

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.

53

Describe how nicotinic receptor changes during development

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

54

functions of neurotrophins

survival, synapse elimination, synapse plasticity