things I don't understand (8-10)

Question 1

describe the process of Wnt signalling

Answer 1

1. Wnt binds to frizzled and LRP
2. LRP’s cytoplasmic tail phosphorylates axin
3. the Beta-catenin, GSK3 and APC complex is destabilised = release of beta-catenin
4. beta catenin translocates to the nucleus and forms a complex with TCF to activate transcription of target genes

Question 2

what complex is beta catenin held in by axin

Answer 2

beta-catenin, GSK3 and APC

Question 3

what does BMP4 inhibit

Answer 3

neural cells - causes them to differentiate into epidermis

Question 4

what inhibits BMP4 allowing ectodermal cells to differentiate into neural cells

Answer 4

chordin, noggin & follistatin

Question 5

what happens in mice KO for chordin and noggin

Answer 5

BMPs are not inhibited so neural fate is not induced. produces mice without a forebrain, nose or facial structure

Question 6

describe the process of neural tube formation

Answer 6

• Neuroectodermal cells dive down and differentiate into the neural plate
• On either side of the neural plate is a band of cells called the neural crest
• Neural plate invaginates and the neural crest tissue sits at the top = forms the neural groove
• Neural groove pinches off to form the neural tube – neural crest cells combine

Question 7

what do the neural crest go on to produce

Answer 7

neurons of the peripheral nervous system
- depending on positional cues they will become either sympathetic or parasympathetic

Question 8

what is required for fusion of the neural plate

Answer 8

adhesion molecules - N-CAM and N-cadherin

Question 9

where do neural stem cells come from

Answer 9

the ventricular zone of the neural tube

Question 10

what forms radial glia

Answer 10

neuroepithelial cells under the influence of FOXG1/HX2/PAX6

Question 11

name 2 Wnt inhibitors

Answer 11

dickkopf & Cerberus

Question 12

where are Wnt inhibitors made

Answer 12

by the dorsal anterior mesoderm

Question 13

what are Wnt inhibitors important for, how do we know?

Answer 13

establishing neuroectodermal tissue

• ectopic placement of Cerberus results in the formation of a secondary head structure

Question 14

where is FGF and RA found in high conc

Answer 14

FGF = posterior
RA = central mesoderm in the middle of the embryo

Question 15

what do dorsal neurons of the spinal cord form

Answer 15

sensory neruons

Question 16

what do ventral neurons of the spinal cord form

Answer 16

motor neurons

Question 17

the anterior part of the neural tube divides rapidly to form three primary vesicles - what are they?

Answer 17

the forebrain midbrain and hindbrain

Question 18

what part of the forebrain curls up to form a three pronged structure, what does it develop into

Answer 18

telencephalon - develops the cerebral cortex

Question 19

what does the midbrain form

Answer 19

vision, hearing and motor control

Question 20

what does the hindbrain form

Answer 20

cerebellum, medulla and pons

Question 21

what do the first neurones to arrive in the pial surface form

Answer 21

the pre plate

Question 22

when the first wave of cortical plate neurons arrive, they split the preplate into what 3 zones

Answer 22

marginal zone
cortical plate
subplate

Question 23

how can neural stem cells be visualised

Answer 23

they express nestin - so using an anti-nestin antibody

Question 24

how can radial glial fibres be visualised

Answer 24

they express vimentin - using a anti-vimentin antibody

Question 25

what happens when migrating neurons detach from the radial glia

Answer 25

they translocate tangentially to their final position

Question 26

what produces reelin

Answer 26

cajal-retzius cells of the marginal zone

Question 27

what does reelin bind to

Answer 27

very low density lipoprotein receptor (VLDL-R), ApoER2 and integrin receptors

Question 28

what happens when reelin binds

Answer 28

disabled 1 binds to the cytoplasmic tails of reelin receptors, and becomes phosophorylated = downstream signalling cascades result in gene expression and the surface properties of then neuron changing = causing them to migrate

Question 29

what happens in reeler and scrambler mice

Answer 29

the preplate fails to split because neurones are unable to penetrate into it

Question 30

what is doublecortin

Answer 30

a MAP expressed in migrating neurons - mutation to DCX results in poor neuronal migration and lissencephaly (in males) and double cortex syndrome (in females)

Question 31

what is double cortex syndrome

Answer 31

half the cells have a functional copy of DCX and migrate correctly into a layered cortex the other half do not migrate properly resulting in bands of grey matter between the ventricle and cortex

Question 32

name 2 locations of adult stem cells

Answer 32

dentate gyrus lining of lateral ventricles in the sub ventricular zone

Question 33

name the 3 domains of the axonal growth cone

Answer 33

1. central domain 2. transitional domain 3. peripheral domain

Question 34

give an example of where semaphorin is expressed

Answer 34

the ventral part of the spinal cord secretes semaphorin 3 to repel thermoreceptor and noiceptor neurites

Question 35

name a contact repulsant

Answer 35

ephrin

Question 36

give an example of where ephrin is involved

Answer 36

retinotopic map formation = nerve cells in the retina send out projections to the tectum (superior colliculus in mammals) that directs eye movements. Temporal retinal neurons have high sensitivity to ephrins (repelled). Nasal retinal neurons have low sensitivity to ephrins and so extend to a higher concentration of ephrins.

Question 37

what factor is needed for neural survival

Answer 37

brain derived neurotrophic factor

Question 38

describe a dystrophic defect

Answer 38

spinal bifida = the spinal cord and its meninges herniate through a defect in the vertebral column - early surgical repair increases changes of survival - affected infants can have motor and sensory deficits

Question 39

describe lissencephaly

Answer 39

(lack of neural folds): brain surface is smooth due to failure of neuronal migration affected children have small brains and often develop intractable seizures, with severe impairment of neurological development