9. Neural Development

Question 1

where does neural stem cell replication occur

Answer 1

in the ventricular zone of the neural tube

Question 2

for a neuroepithelial cell to produce radial glia, what genes must it be under the influence of

Answer 2

either:
FOXG1
HX2
PAX6

Question 3

what are radial glia used for

Answer 3

neuronal migration

Question 4

where does the neural tube begin closing up

Answer 4

in the middle (think of it like a burrito)

Question 5

what are the openings of the neural tube called

Answer 5

anterior and posterior neuropores

Question 6

which neuropore of the neural tube closes up first

Answer 6

the anterior neuropore closes on day 25
the posterior neuropore closes on day 27

Question 7

what are somites

Answer 7

bilaterally paired blocks of mesoderm that form along the head-to-tail axis

Question 8

what signalling molecule determines the anterior-posterior axis

Answer 8

Wnt

Question 9

what is Wnt signalling role in the dorsal-ventral axis

Answer 9

Wnt specifies the Nieuwkoop centre by allowing beta-catenin release and translocation

Question 10

name 3 Wnt inhibitors

Answer 10

dickkopf
cerberus
insulin-like growth factor

Question 11

what are Wnt inhibitors also known as

Answer 11

paracrine factor antagonists

Question 12

what produces Wnt inhibitors, why?

Answer 12

the organiser and dorsal anterior mesoderm

this allows neuroectodermal tissue to be established

Question 13

what is the evidence for the role of Cerberus in allowing neuroectoderm development

Answer 13

ectopic placement of Cerberus during early gastrulation produces a secondary head structure

Question 14

where is Wnt found in high concentrations

Answer 14

the ventral, posterior aspect

Question 15

what 2 molecules are important in anterior-posterior patterning

Answer 15

fibroblast growth factor (FGF)
retinoid acid

Question 16

where is fibroblast growth factor found in high concentrations

Answer 16

in the posterior end
(it is degraded at the anterior)

Question 17

where is retinoic acid found in high concentrations

Answer 17

high concentrations in the middle of the embryo

Question 18

where is retinoid acid made

Answer 18

by the central mesoderm

Question 19

what do FGF, RA and Wnt signalling all regulate

Answer 19

Hox gene expression - these genes act as positional cues

Question 20

what two gradients control torso-ventral patterning

Answer 20

Wnt and TGF-beta

Question 21

describe what happens to dorsal neurons of the spinal cord

Answer 21

high Wnt signalling instructs them to become sensory neurons

Question 22

describe what happens to ventral neurons of the spinal cord

Answer 22

low concentrations of Wnt signal to them to become motor neurons

Question 23

what happens to the anterior part of the neural tube in the first stages of brain development

Answer 23

the anterior part divides to form three primary vesicles:
the forebrain, midbrain and hindbrain

Question 24

what happens to the forebrain? what does it go on to form?

Answer 24

it curls up to form a three pronged structure that develops into the cerebral cortex

Question 25

what happens to the posterior part of the neural tube

Answer 25

it forms the spinal cord

Question 26

what does the midbrain go on to form

Answer 26

vision, hearing and motor control

Question 27

what does the hindbrain go on to form

Answer 27

the medulla, pons and cerebellum

Question 28

how many layers is there in the cerebral cortex

Answer 28

6

Question 29

what is the internal and external layer of the cerebral cortex

Answer 29

the external layer is the molecular layer the internal layer is the fusiform layer

Question 30

describe pyramidal neurons

Answer 30

cell body is a triangular shape they have extensive up reaching dendrites typically glutamatergic neurons

Question 31

describe the movement of the first cohort of post-mitotic neurons

Answer 31

moves up from the ventricular zone towards the pial surface to form the preplate

Question 32

how do post-mitotic neurons get transported

Answer 32

across the radial glial cell scaffold

Question 33

the first wave of neurons arrive in the prelate, what then happens?

Answer 33

the prelate is split into three zones: 1. marginal zone 2. cortical plate 3. subplate

Question 34

what do neural stem cells produce

Answer 34

nestin

Question 35

cortical plate neurons arrive in an inside out sequence, what does this mean?

Answer 35

the earliest born neurons become layer 6 and the last to arrive become layer 2

Question 36

how can we visualise neural stem cells

Answer 36

using an anti-nestin antibody

Question 37

what type of protein is nestin

Answer 37

an intermediate filament protein

Question 38

what do immature glial cells (including radial glial cells) produce

Answer 38

vimentin

Question 39

how can we visualise radial glial fibres

Answer 39

using aan anti-vimentin antibody

Question 40

how do neurons migrate towards the target area

Answer 40

they detach from radial glia and can translocate tangentially to their final position

Question 41

what is reelin

Answer 41

an extracellular matrix-associated glycoprotein

Question 42

what type of cells secrete reelin

Answer 42

cajal-retzius cells

Question 43

where are cajal-retzius cells found

Answer 43

in the marginal zone

Question 44

where is reelin secreted by the cajal-retzius cells

Answer 44

cajal-retzius cells have ascending processes which contact the pial surface and secrete reelin

Question 45

name 2 receptors reelin binds to

Answer 45

very low density lipoprotein receptor (VLDL-R) apolipoprotein E receptor type 2 (ApoER2)

Question 46

what happens once reelin binds to the receptor

Answer 46

disabled 1 binds to the cytoplasmic tail of the receptor and gets phosphorylated downstream kinase signalling results in gene expression that drives migratory behaviour

Question 47

what happens in reeler and scrambler mice

Answer 47

the preplate fails to split because new neurons are unable to penetrate into it

Question 48

what are reeler and scrambler mice

Answer 48

mice that are null for reelin and disabled 1

Question 49

what is human reelin mutation linked to

Answer 49

lissencephaly and autism

Question 50

how can you visualise preplate neurons

Answer 50

staining with chondroitin sulphate proteoglycans

Question 51

some stem cells are retained in the human brain, give 2 examples

Answer 51

dentate gyrus stem cells involved in memory doublecortin - expressed by immature neurons

Question 52

what part of disabled 1 becomes phosphorylated

Answer 52

the phosphotyrosine interacting domain

Question 53

after Dab1 is phosphorylated, what can it now do

Answer 53

bind to protein tyrosine kinases Src, Abl and Fyn

Question 54

what happens in mutations of the doublecortin gene

Answer 54

defective migration of neurons results in poorly organised layers of the cortex = double cortex syndrome or lissencephaly dependent on gender

Question 55

why does the pathology associated with doublecortin mutations depend on gender

Answer 55

DCX gene is located on the X chromosome, so females have half a functional copy of the gene that results in half the cells migrating correctly, the others do not = double cortex syndrome no functional copy of the DCX protein = lissencephaly

Question 56

how is doublecortin implicated in cancer metastasis

Answer 56

unstable interaction between DCX and microtubules destabilises the cellular organisation = disorganised cell movement

Question 57

what is doublecortin

Answer 57

a microtubule associated protein

Question 58

where is doublecortin expressed

Answer 58

in migrating neurons of the CNS and PNS during embryonic and postnatal development

Question 59

why do neural crest cells become peripheral neurons and ganglia

Answer 59

because they have a low affinity for neurotrophic p75 receptor

Question 60

what produces radial glia progenitor cells

Answer 60

neuroepithelial stem cells

Question 61

where do neural stem cells develop from

Answer 61

the ventricular zone of the neural tube

Question 62

name 3 things neural stem cells go on to produce, which first

Answer 62

neurons astrocytes oligodendrocytes

Question 63

what is the role of SOX2 what happens if there is a loss of SOX2

Answer 63

maintaining neural stem cells loss of SOX2 = causes the cell to exit the cell cycle

Question 64

what is the role of SOX1 and SOX3

Answer 64

regulate neural progenitor cell states

Question 65

why is there not many stem cells in the adult brain