Exam 2: Chapter 4 Flashcards
How do you know if neuron development is intrinsic or extrinsic factors?
Transplant in dish
If changes due to knew environment: extrinsic
No change: intrinsic
Elegans and Chalfie’s touch insensitive mutants. What is normal?
Q –> Q 1 A and Q1P
Q1P goes on to become touch cell and interneuron
Unc-86 Elegans mutant
Q’ instead of Q1P
This makes Q7’a and Q’’
No touch cells, no interneurons
Mec-3 Elegans mutant
Q –> Q1P
Interneurons, but no touch cells
Touch sensitive but don’t differentiate
Mec-7, 12, 17
Defective touch cell, touch insensitive
Huckebein is activated by ___ and inhibited by __-
activated: Wnt/shh
inhibited: engrailed/gooseberry
homobox genes: msh, ind, vnd follow
Dpp gradient D-V
msh: high Dpp concentration, most Dorsal
What are the differences between 1st and later GMCs?
Earlier: deep in CNS, long axons
Later: Short axons, on edge
Order neuroblasts send to mother cells:
Pdm, Krueppel, Hb, Castor
Hb -> KR -> Pdm –> Cas
Ko Hb
no hunchback, but others are ok
Ko Kr
Skip that step
Pdm too early
Skip Kr
Asymmetric cell division
1) Par complex apical side
2) Localized Numb
3) Inscruitible and PINS
4) LGL replaces Baz
5) Miranda traps prospero, which turns on GMC genes
Par complex made up of
1) Bazooka
2) Par-6
3) aPKC
Why does Numb need to go to GMC?
inhibits other pathways to let mother cells divide and make 2 neurons. If it stays, inhibits neuroblast division.
What does inscrutable and PINS do?
attract miotic spindle fibers that direction and orient division.
What phosphorylates Baz so it leaves?
Aurdura A
What phosphorylates LGL so it can replace Baz?
aPKC
Why does LGL replace Baz and Numb-phosphorylated?
Numb-P and has oriented spindles, but needs everything on GMC side.
Numb-P inhibits notch pathway
What traps prospero and what does prospero do?
Miranda
Prospero- turns on GMC genes
What inhibits Numb/Prospero on basal?
GMC
What pulls up phosphorylated Numb?
PON
Sp1 (SOP)–>
Sp2b- anterior (dominant)
Sp2a- posterior
Sp2b vs. Sp2a
Sp2b inhibits Sp2a by notch pathway
if ablated, Sp2a becomes Sp2b
Sp2a/b in notch mutant (KO notch)
2x Sp2B
Sp2a/b in notch increase mutant
2x Sp2a
Sp2b –>
Neuron and support cell
Neuron inhibits support cell by notch
Sp2a –>
Socket and Shaft
Socket inhibits Shaft via notch
What is Sp2b not effected by notch?
NUMB in Sp2B inhibits it.
Sevenless Pathway
Boss - ligand
Sev- receptor
Boss –> Sev –> MapK (erk) –> Yan and Prkd –> R7 program.
R7 in 7less path
UV sensitive, last to join/differentiate
Has the Sev receptor, needs BOSS ligand from R8
Neural lineage in drosophilia is determined by
lateral inhibition (notch/delta) neuronal fate = transcription factors
Why asymmetric division?
Allow for functionally linked cells with identity
Chicken and Quail transplant of cholinergic and adrenergic neurons
V: S7, Cholinergic (para)
T (low): S18, adrenergic neurons (sym)
If transplants to wrong area, respond to environment cues to become the other.
Wnt (late)
Sensory
BMP2/4 and CTGF beta 1-3
ANS
Nrg-1
Schwann (glia)
Nrg vs. Ngn
Nrg- neuregulin, secreted by neurons
Ngn- neurogenin, proneural
BMPs in dorsal aorta (sym ganglia) –>
Mash1 and Phox26
Mash 1
proneural bHLH transcription factor
creates neuron specific stuff
turns on neuron program, gets neurofilaments/microtubules you need to stabilize axons/dendrites
Phox26 –>
TH- rate limited step in dopamine production
D-beta-H: makes NE
Early Wnt
Sensory and BHLH/Nrgn2, needs early wnt to get here
FGF
Neurites to come off.
Encourages microtubules
Encourages TH/DBH
Turns on NGF Receptor - Can’t Skip this step!
Once FGF activates NGF, what does that do?
acts on NGFR, fully differentiate/survivor
sym neuron survival
Fully differentiate neurons release ___ for next cells
Neurogenin
Remove wnt in environment;
no sensory neurons, but you can make everything else respond to future signals even though you missed the first.
Don’t control duration/location of signals:
wnt too big/long signal, more cells stuck and can’t migrate on, lose too many neurons, stuck in wnt cycle.
If you culture Arota + neural crest OR BMP7 + neural crest, what happens?
Adrenergic neurons (NE)
Rodent Feet: Hairy vs. Foot Pads
Hair- no sweat, NE
Foot Pad- sweat, acetyl
How does foot pad work?
release NE, stop at target
Food pad releases CNT/LIF to change phenotype
acetyl program on: CAT (acetyltransferase)
NE program off (TH/DBH)
Experiment with sweat glands on hairy skin and parotid gland tissue:
sweat glands: cholinergic
parotid: NE (adrenergic)
Matches transplant
Nrg-1 makes glia by…
telling newcomers you’re too late: no more neurons. More Nrg-1= more likely glia. More neurons = more cells making it.
Experiment: Crest cell ganglia treated with +Nrg-1 or delta
Mostly Glia, 10% neuron
Experiment: crest cell ganglia, treated with -NRG-1 and +BMP2
Mostly Neuron, 80%
Cortical Layer Experiment: Layer 6 –> Layer 321
Becomes 321
Cortical Layer Experiment: Layer 321 –> Layer 6
Becomes, 321, too late to change, fate is becoming determined
Cortical Layer Experiment: Layer 54 –> 321
Becomes 321
Cortical Layer Experiment: Layer54 –> Layer 6
Becomes 54
Lateral/Dorsal
Sensory
Medial/Ventral
Motor
___ and Ultimately ____ will turn on certain classes of homodomain genes which repress to one subdivison, new regions, newfactors, things slide around, add across board, see what you can make where.
BMP and ultimately RA
