exam 2 Flashcards
neurosurgery
t or f the retina cannot act as an organizer
false
eye is a neural tube. an outgrowth of the _____ (region of brain)
diencephalon
cilia and flagella can only be on the ______ surface of the epithelial cell
APICAL
sensory cells must have their apical surface facing toward or away from the fluid environment that the sensation moves through?
TOWARD
fluid is gone from what structure in the MATURE eye
optic vesicle
organize chronologically:
Retina, optic vesicle, optic cup
lens pit, lens placode, lens, lens vesicle
optic vesicle > optic cup > retina
lens placode > lens pit > lens vesicle > lens
retinal cell division takes place on the _____ side of the _____ layer and daughter cells that leave delaminate by penetrating _________
retinal cell division takes place on the APICAL side of the EPITHELIAL layer and daughter cells that leave delaminate by penetrating the BASAL LAMINA
individual cell clones are shown to extend linearly in the retina. Does this finding show that the cells are migrating VERTICALLY or HORIZONTALLY
Vertically, like in the cortex. from apical layer to granule cell layer
t or f. when following a progenitor cell on its clonal migration pathway in the retina, you should expect to see one cell type all the way through
false. vertical migration of progenitor clones results in multiple cell types (photoreceptors, neurons, glia), showing that these retinal progenitors are multipotent
in retina, expect what cell type to appear first, and what type to appear last? RPC, Ganglion, Muller glia
first= RPC and ganglion last= muller glia
a retinal progenitor cell that is NOT exposed to Neurogenin 2 cannot differentiate into _____. A retinal progenitor cell that is exposed to neurogenin 2 can differentiate into ______
NO neurogenin2 = NO retinal ganglion cells. bHLH TF
(but can differentiate into all other retinal cell types)
Yes neurogenin2= differentiation into ALL retinal cell types including Retinal ganglion cells
in retina, is neurogenin2 seen to be present early or late in development? explain
EARLY. Neurogenin 2 allows for differentiation of RPCs to retinal ganglion cells, the first cell group to usually show up in differentiation.
a retinal progenitor cell that is exposed to more neurod1 and math3 than math5 is directed toward what cell fate? how about vice versa?
\+++neurod1/math3 = amacrine cell \+++math5 = Retinal ganglion cell
what protein concentration remains constant during retinal development and is indicative of formation of late-born types?
[Casz1] remains constant throughout retinal development but is inhibited in early developmental stages by Ikaros. since there is less ikaros later on, there is more ACTIVE casz1, causing more late-born types
[casz1] remains constant throughout retinal development, but is inhibited in early developmental stages by ____
Ikaros. A KO of ikaros yields very few early-born types.
the presence of an miRNA that silences Ikaros would result in _____ (retinal development)
low amount of early born type cells, large amount of late born type cells due to increased activation of Casz1
t or f retinal cell fate is entirely stochastic
false, it is stochastic but the probability of a particular fate is the same as the proportion of that cell type in the mature retina. Weighted die
avian high acuity area (HAA) is specified by high concentrations of what and low concentrations of what
+++[cyp26] +++[FGF8] —[RA]. This area is devoid of rods and packed with cones. If retinoic acid is added to this area with an inhibitor of RA degradation, rods will be present in this area. This is just an example of the fact that there may be inherent biases in the strength of certain repressors over others
intracellular signalling for axon guidance particularly targets _____-based motility.
actin-based motility.
ECM molecules signal for changes in direction (attraction and repulsion) via various _____
integrins
cell-cell contact for axonal guidance- CAMS and cadherins are usually (positive or negative) signals for growth cone motility
positive (permissive)
cell-cell contact for axonal guidance- semaphorins and ephrins are usually (positive or negative) signals for growth cone motility
negative. Repulsive signals that cause the growth cone to stop. Doesn’t allow axon to grow past its correct target
t or f ephrins and eph receptors are an example of bidirectional signalling because binding of the two can cause cleavage of both
true
netrin-DCC signaling (attracts or repels) growth cones
attracts. diffusible signal
slit-robo signaling (attracts or repels) growth cones
repels. diffusible signal that causes growth cones to stop
axonal guidance- what neurons form a segmental ladder organization of the nervous system. they form what will become the major longitudinal tracts and commisures (rungs of ladder)
PIONEER NEURONS
retinal afferent (PIONEER) neurons normally project posteriorly through the diencephalon to the optic tectum (midbrain), if these are transplanted posterior to the tectum, where will they project? why?
pioneer neurons will project posteriorly still through the spinal cord dorsal white matter because they respond to global cues
If there is a semaphorin bridge that a pioneer axon must cross, and the guidepost cell on the other side of that bridge is missing, what will happen with the axon?
the axon will NOT cross the bridge, and will end up searching randomly for another guidepost cell on the original side of the bridge. semaphorin is a repulsive cue that cannot be crossed without a guidepost cell present for the pioneer
a fasciculin II KO would cause what in growth cone guidance
axons that are following other axons by cell-cell communication (fasciculation) will not be able to follow anymore and will not grow in a tract. will grow randomly
t or f neurons prefer certain substrates, and will grow to follow that substrate more often than cutting across a less preferred one
t. this is called adhesivity as a guidance cue. This correlation is really only present in ARTIFICIAL substrates
Why does semaphorin from the presumptive epaxial muscle direct LMC motor axons to the limb but not MMC? where does MMC go and why?
MMC motor axons go straight to presumptive epaxial muscle because the LHX3 that is expressed in them represses semaphorin receptors so repulstion does not occur. LHC motor axons have the semaphorin receptors so they are repressed from taking a route to innervate that muscle and are directed to the limb instead
LMC muscle innervation. In a Lhx1 KO, what region is not innervated?
dorsal portion is not innervated
LMC muscle innervation, what side of the body (D or V) does the LMCm innervate? what transcription factor causes this? how about LMCl?
LMCm= ventral, TF is Isl1 LMCl = dorsal, TF is Lhx1
an Ephrin knockout causes LMCl axons to innervate what region?
the ventral limb and NOT the dorsal limb anymore. Ephrin repels LMCl axons from the ventral limb
how does semaphorin repel LMCm axons from the dorsal limb?
LMCm axons produce neuropilin still after reaching their lateral region. LMCl axons reduce expression of neuropilin (a receptor of semaphorin) so they are not repelled by the semaphorin dense dorsal limb region. The ventral region has practically no semaphorin, so the LMCm is repelled by the dorsal region to here
why when the frog eye is taken out and rotated 180, does the temporal projection still go to the anterior tectum and the nasal projection to the posterior tectum?
cell membranes from the POSTERIOR tectal neurons REPEL axons from the temporal retina ganglion cells. they will always stay away from posterior tectum. High ephrin in the posterior tectum, high Eph in the temporal retina ganglion cells. Nasal retina ganglion cells have low eph, so they can reach the posterior tectum, whereas the temporal cells are stuck reaching only the anterior
forcing nasal retinal ganglion cells to express Eph will cause them to project to what area of the superior colliculus?
anterior (rostral). the superior colliculus has an ephrin concentration gradient with high concentration in the posterior (caudal) tectum
AXON GROWTH: Stabilizing microtubules are _____ (tyrosinated or acetylated)
acetylated
what happens when a filopodium encounters a permissive substrate?
the clutch is engaged- substrate is coupled to actin via a transmembrane receptor or something, so the actin is locked to that membrane site and can only grow forward, not be recycled backward. growth cone protrudes, cytoplasm and organelles fill up new C domain area, microtubules tighten up to form mature axon shaft
F-actin retrograde flow causes what for dynamic microtubules
clears dynamic microtubules from the P-domain. no longer exploratory because the engine is in idle
Cdc42 and Rac1 are what types of cues? do they repel or attract the growth cone
cdc42 and rac1 activate the growth cone. attractive
RhoA is an attractive or repulsive cue for the growth cone?
RhoA deactivates the growth cone. retract/repel
increased Ca2+ in the growth cone causes what
an attractive cue, cone turns toward that cue
TRP channel blocker in the growth cone causes what response for Ca2+? what happens to growth cone activity
growth cone does not respond to attractive cue (ie netrin, BDNF), no influx of Ca2+
what type of cells know how to delaminate for migration purposes
only IMMATURE NEURONS know how to delaminate from neurogenic epithelia (Neural crest)
Ephrin blocks neural crest cell migration across (anterior or posterior) somite
posterior. neural crest cells have eph receptors so will avoid high ephrin concentration in posterior somite
melanocytes, parasympathetic ganglia, enteric ganglia, sensory ganglia (dorsal root ganglia), sympathetic ganglia, and chromaffin cells are all derived from _________
trunk neural crest
if you put a quail cholinergic neural crest cell in a chick adrenergic neural crest region, what will likely happen to the cell
it will become an adrenergic fated cell, unless it is a PREDETERMINED neural crest cell- wont give new phenotype upon transplant
a neural crest cell that is constantly exposed to neuregulin will become _______
a schwann cell
a neural crest progenitor that is exposed to LIF (leukocyte inducing factor- in the dorsal somite) will become
a sensory neuron
a neural crest progenitor that is expressed to ______ (a notochord factor) will become a sympathetic progenitor. What will happen if that progenitor is exposed to NGF? CNTF (ciliary neurotrophic factor)?
FGF2. exposure to NGF would cause formation of an adrenergic neuron (releases NE) in the adrenal medulla. exposure to CNTF would cause formation of a cholinergic neuron (think Cholinergic Neuron Transcription Factor)
a neural crest progenitor that is exposed to glucocorticoids from the developing adrenal cortex will become a ________ and needs exposure to glucocorticoids to become a full fledged ______. If this first cell is exposed to NGF it will become adrenergic instead. What does the glucocorticoid cell ultimately produce and from where?
chromaffin cell progenitor -> chromaffin cell
produces Epinephrin because they produce an enzyme that changes NE to E (unlike adrenergic neurons) for blood stream communication from adrenal medulla
sweat gland derived _____ instructs sympathetic afferents to use Ach instead of _____. turns the sympathetic progenitor into a cholinergic neuron instead of an _____ neuron
CNTF, NE, Adrenergic. TARGET DERIVED FACTOR CAN INDUCE DIFFERENTIATION
schwann cells that encounter BMPs from cells that desire ______ innervation respecify as ________ neurons
parasympathetic, parasympathetic
____ gradients regulate neuronal specification and neurogenesis in the inner ear
FGF
T or F the cochlear (spiral) ganglion neurons and Scarpa’s (vestibular) ganglion neurons originate from the same region
T, it is a region defined for delamination
how does the mature neuron area of the inner ear suppress extra maturation activity of the transit amplification area and the specification/delamination area?
as the mature neuron area grows, it produces more FGF5, which suppresses the activity of the other areas.
if you elevated the FGF level of the mature neuron area prematurely, what would its size be respective to the Transit-amplification area? how about if you kept the FGF5 concentration of the mature neuron attenuated (low)?
if the FGF5 concentration was kept low, the transit-amplification area would keep feeding neurons to the mature neuron area and it would grow indefinitely. if the FGF5 concentration was prematurely HIGH, the transit-amplification area would be much larger than the mature neuron-area, because the neurons in the TA area would not be allowed to mature
what factor is characteristic of dorsal otic vesicle? ventral? Pax2/SHH, Otx2, Wnt2/Gbx2, Hmx3
Pax2/SHH (SHH from notochord) and Otx2= ventral otic vesicle (think O P)
Wnt2/Gbx2 and Hmx3= dorsal
look at and probably draw slide 44 on development- neural crest & placodes
yes
a Pax2 KO will do what to inner ear development?
loss of cochlea (ventral)
an otx1 KO will do what to inner ear development?
loss of lateral semicircular canal
an Hmx3 KO will do what to inner ear development?
loss of dorsal half (vestibular portion)
KO of Pou4f3 will do what during inner ear development
loss of hair cells (its a transcription factor)
ko of Hoxa2, hoxa1/hoxb1, kreisler, fgf3 will do what during inner ear development
total loss of inner ear
an otic vesicle cell exposed to neurogenin1 becomes
a neuron
an otic vesicle cell exposed to Atoh1 becomes
a hair cell
an otic vesicle cell exposed to Hes/Hey/Id becomes
a supporting cell
an atoh1 KO has what problem
no hair cells
spiral ganglion neuron development is fucked up upon _____ KO
neurogenin1
a wild type hair cell progenitor becomes a hair cell because why? (notch and Atoh1)
What if a person is a notch pathway mutant?
a wild type hair cell progenitor has Atoh1 to suppress notch. the cells lacking atoh1 differentiate as supporting cells
The notch pathway mutant has a fuck ton of hair cells because there is no notch to suppress it from becoming a sensory cell
inhibitory and excitatory cns neurotransmitters. how many active zones per synapse?
in cns, one active zone per synapse. GABA/Glycine inhibitory, glutamate excitatory
T or F there are hundreds of active zones per 1 neuromuscular junction. What is the primary neurotransmitter?
true, primary neurotransmitter is ACh.
which region can have axons with synapses on the shaft rather than just at the axon terminal
NMJ at axon terminal only
CNS can have axons at SHAFT
t or f each muscle fiber is innervated by 100s of axons
f. each muscle fiber is innervated by one motor axon, but each motor axon innervates multiple fibers (one motor axon + every unit it innervates = one motor unit)
what labels active zones in imaging and what labels AChRs: alpha-bungarotoxin (red), Bassoon (green)
alpha-bungarotoxin (red)= AChRs, Bassoon (green)= active zones
in a basic sense, what happens to AChR transcription and shit like that at a new NMJ synapse? (include discussion of nuclei)
Nuclei directly under the synapse are activated to transcribe more AChR mRNA, nuclei outside of the synapse are repressed from that. AChRs cluster beneath the synapse
what would happen to extrasynaptic nuclei in a muscle if the axon innervating it were paralyzed
they would no longer be repressed from transcribing AChRs
what would happen to extrasynaptic nuclei if a muscle fiber were denervated? What if that denervated fiber were then electrically stimulated at the synapse?
the nuclei would no longer be repressed from transcribing AChRs, until electrical stimulation, which causes them to return to their states of repression
only ______ produce Z+ agrin, which is 1000x more potent than Z-
motor neurons
original agrin hypothesis. agrin is released by presynaptic neuron and binds to ____ which activates MuSK, that produces _____ an adaptor protein that clusters AChRs
Lrp4 activates MuSK which cascades to make Rapsyn which clusters receptors
t or f an agrin knockout will still create synapses even though it cannot cluster receptors
t
what will happen to an NMJ in a musk KO? Lrp4?
both will produce no synapses
what will happen to an nmj with a rapsyn ko?
effector will be clustered (Agrin Lrp4/MuSK complexes)
t or f a group of muscle cells in culture will still make an AChR receptor cluster similar to that in vivo without innervation if basal lamina is not present
false. This would all be true if the basal lamina components WERE present. This suggests that the nerve isnt as important for receptor clustering as we thought
t or f before the agrin hypothesis, it had already been noted that AChR clusters occur early in development before the nerve even arrives
t, clusters form early w/o nerve but seem to get dispersed later by the nerve, which stabilizes “real” nmjs via agrin
t or f, following a nerve growth time lapse, it appears that clusters occur in the path of the nerve after the nerve has reached its destination
false, it appears that the nerve actually follows an AChR cluster pathway in its growth
So, agrin KO has no receptor clusters. how is this phenotype rescued back to WT? think the pathway
by knocking out choline acetyltransferase (ChAT), which blocks ACh release. Seems that ACh keeps receptors from clustering when not in the presence of agrin
______ binds phosphotyrosine binding domain on MuSK, inducing AChR clustering pathway WITHOUT AGRIN
Dok-7
what happens to the NMJ in a Dok-7 KO. think about what dok-7 be doin my hitter
dok-7 clusters AChRs without the presence of agrin. So the nerve-independent early clusters will be lost along with the later true NMJ clusters. So the nerve cant even follow the cluster path when growing anymore
NEW AChR cluster hypothesis. not just agrin
Dok-7 binds MuSK and activates rapsyn pathway for nerve independent clustering. Once a nerve reaches the cluster, a synapse begins forming. Agrin is released from the presynaptic cell along with ACh. ACh leaving the SYNAPSE represses extrasynaptic receptors via causation of endocytosis. The agrin released from the presynaptic cell saves the clusters beneath the synapse from the released ACh by continuing to FULLY activate the MuSK pathway
if you crush the muscle but leave the ghost of the basal lamina, can the nerve still make the same NMJ? how
yes, there is a special orgainization of LAMININ that the nerve follows- appears only at synapses
what type of laminin does not exist beneath the active zones? what happens if this is knocked out?
alpha-4, a KO causes inability of synapse to line up active zones to junctional folds
what type of laminin KO causes loss of folds and active zones?
beta2 KO because beta2 laminin is present in all synaptic lamina
what type of laminin KO causes a smaller overall synapse but ok structure with paired up active zones and junctional folds
alpha 2
what binds the presynapse to laminin at NMJ?
voltage dependent calcium channels. organizes the terminals
Grays type 1 synapse- asymmetric or symmetric? excitatory or inhibitory? spherical or flattened vesicles?
asymmetric, excitatory, spherical
Grays type 2 synapse- asymmetric or symmetric? excitatory or inhibitory? spherical or flattened vesicles?
symmetric, inhibitory, flattened
what receptor type is clustered by Gephyrin? PSD-95?
Gephyrin-Inhibitory glycine receptors
PSD-95- Excitatory glutamate receptors
What domain protein is the most important for synaptic scaffold?
PDZ domain- P! SD-95, D! iscs large, Z! onula occludens-1= P. D. Z.
PSD-95 proteins acts as scaffolds to coordinate the ____ density
postsynaptic density
what scaffolding protein is required for inhibitory synaptogenesis? is it a PDZ protein?
gephyrin is NOT a PDZ protein. without gephyrin the animal is at full flex as if it were injected with strychnine
step 1 after axodendritic contact (synaptic formation process)
presynaptic terminal leads process and assembles its machinery. PRESYNAPTIC DIFFERENTIATION SEEMS TO PRECEDE POSTSYNAPTIC DIFFERENTIATION
what is presynaptic and what is postsynaptic neurexin and neuroligin
neurexin= presynaptic neuroligin= postsynaptic
cadherin needs what to stick out like a rod for cell-cell adhesion. does it mediate homophilic or heterophilic interactions?
Ca2+. mediates homophilic interactions
cadherins signal to the cytoskeleton via ______
the armadillo proteins alpha and beta catenin
after cadherin interaction, why does alpha catenin interact with actin branches to form actin bundles?
stabilizes cytoskeleton so cells stay w/o ruining their junction
are cadherin junctions in the middle of the active zone or do they flank it?
they flank it
what would happen if a growing axon had its cadherin functions blocked by AB?
it would grow past its target site. N-cadherin tells cell where to STOP
cadherins have an adhesive code since there are like 20 types a mixture of the types creates a specific target
yes
t or f no spines are formed when cadherin is disrupted because there is no way to adhere to the post synaptic cell
f. Dendritic spines are long AF actually because they cant find their target cell
neuroligin (NLG) 1 is found at excitatory or inhibitory postsynaptic sites?
NLG2?
NLG1= excitatory NLG2= inhibitory
how does an artificial synapse assay work?
place a neuron in culture with cells that express a synaptogenic molecule that appears in post-synaptic cell (neuroligin) and the cell will grow toward it to make artificial synapses. NLG1 induces presynaptic differentiation
NLG and neurexin mutations are great markers for what disorder?
autism
what does a point mutation in NLG1 or NLG3 do to “cause” autism
creates a hypomorph. the molecules are not packaged properly so they are only expressed by about ten percent
t or f, if you ko all NLG molecules, a lesser number of synapses will form and less effective synaptic activity will occur
f. If you KO all NLG molecules, the synaptic number will be maintained, however the synaptic activity will be not well functioning
read synaptogenesis 2 slide 34 and 35
yes
what glial cell type acts as a mediator for synaptic formation
astrocyte- without astrocytes, very few synapses actually form
t or f, synapses without astrocytes to mediate them are abnormal, and there are fewer altogether
f. There ARE fewer altogether without astrocytes, but the present synapses still look normal
what secreted factor from growing astrocytes increases the number of synapses? how does this protein affect activation levels?
thrombospondin from astrocytes promotes synaptic number, but does NOT create active synapses. ASTROCYTES ARE NEEDED FOR ACTIVE SYNAPSES
TSP (thrombospondin from astrocytes) induced synapses are active PRE or POST synaptically
PRESYNAPTICALLY. postsynaptic activation occurs in presence of other astrocyte factors only. presynaptic activation can occur in the presence of TSP alone
What domain type is active in thrombospondins?
EGF-like
what is the necessary TSP receptor for astrocyte dependent synaptogenesis? KO of this prevents astrocyte and TSP promoted synaptogenesis
alpha 2 delta 1
