L17

Question 1

Caspase9-/- mutants have…

Answer 1

…massive brain tumours and are unviable

Question 2

All Ns have…

regards apoptosis

Answer 2

…built in self termination programme (thus many post mitotic Ns lost); to survive N has to receive overriding external signal which comes from target; Ns compete to receive LIMITED amounts of survival factor

Question 3

Limb bud experiment in chick

Answer 3

Remove limb bud and fewer SNs survive, add extra and more survive

Question 4

Survival factors

Answer 4

Neurotrophins, circulating factors, hormones

Question 5

Neurotrophins

Answer 5

All bind with weak affinity to p75NTR (apoptosis promoter); each binds to preferred TrKR to prevent apoptosis; some Ns generate truncated B/C Rs (promote apoptosis); signal via MAPK pathways thus FGF like GFs also promote survival
(NGF, NT-3, BDNF, NT-4)

Question 6

Cytokines

Answer 6

LIF, CNTF, ILs; if any added after limb bud removal, help to prevent cell death; signal via JAK-STAT pathway

Question 7

Hormones

Answer 7

Circulating testosterone taken up by some Ns, and converts it into oestrogen using aromatase; in some regions of the hypothalamus T is crucial for survival- retains male specific, removes female specific

SDN-POA is larger in males than in females, (m more T, f more estradiol) (vm Hypothalamus)

Question 8

Survival factors …

Answer 8

Trigger Bcl-> inhibit caspase, prevent apoptosis
If none: Bad, Bax activated -> caspase9 activated …
NGF activates Bcl2 -> phospho-inactivation of Bad, Bcl2 also maintains mitochondrial membrane

Question 9

Caspase9 also used for…

Answer 9

…local pruning

Question 10

What is involved in neuronal remodelling during fly metamorphosis?

Answer 10

Caspase3