Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
117 Cards in this Set
- Front
- Back
|
What is the difference between necrosis and apoptosis?
|
Apoptosis: programmed cell death
Necrosis: cell death from damage |
|
|
What is the TUNEL technique and what is it used for?
|
Terminal Transferase UTP nick end labeling identifies dying cells by tagging free nucleosides
|
|
|
What two processes are necessary for initiation of cell death?
|
RNA transcription and protein synthesis
|
|
|
Does blocking synaptic transmission prevent normal cell death, why?
|
Yes because neurons need to receive apoptotic signals from ganglia
|
|
|
Naturally occurring cell death can be preceded by |
Fulfillment of transient function |
|
|
What structure was implanted to investigate cell death in embryos?
|
Limb buds
|
|
|
Does cell death occur more often in larger or smaller targets
|
smaller
|
|
|
What is the neurotrophic hypothesis?
|
Amount of a neurotrophic factor at target site will control the degree of neuron degeneration
|
|
|
How is cell death specified in c elegans?
|
Genetically, via programmed lineage
|
|
|
What happens to cells that express ced-3?
|
They will undergo apoptosis due to transcription of caspases
|
|
|
What other ced proteins are there and how do they interact?
|
ced-3 ced-4 and ced9
ced 3 and 4 are both necessary for cell death ced-9 rescues cell death regardless of c3 or 4 |
|
|
What is the ced pathway?
|
c9 inhibits activating factor c4 which will target the effector protease c3 to create caspases
|
|
|
Has this system for apoptosis diverged between species?
|
No these genes are highly conserved
|
|
|
What is NGF and how was it discovered?
|
Neurotrophin, discovered in sarcoma tissue of chick embryos
|
|
|
What neurotrophins bind to TrkA receptors?
|
NGF and NT3
|
|
|
What neurotrophins bind to TrkB receptors?
|
NT3
|
|
|
What neurotrophins bind to TrkC receptors?
|
NT3 and BDNF and NT4/5
|
|
|
What neurotrophins bind to p75 receptors?
|
proNGF
|
|
|
What two events occur in these receptors after ligand binding that allow it to signal downstream? |
Autophosphorylation, and then phosphorylation of assoc. signalling proteins |
|
|
What is the MAPK pathway activated by and what does it increase transcription of?
|
Activated by ras and increases transcription of Bcl-2 (ced9)
|
|
|
What cellular processes are required for axonal development?
|
Cytoskeleton cycling, movement of vesicles to growth cones, formation of growth cone appendages
|
|
|
What structures allow for formation of visual fields? How did Sperry manipulate these in his experiments?
|
The tectum, sperry switched the orientation of the tectum in fly eye, found that neurons will still grow to proper targets
|
|
|
What is the chemoaffinity hypothesis?
|
Target cells have some sort of biochemical identification tag that allows axons to find their appropriate targets via affinity
|
|
|
What are the two appendages that can be found in growth cones?
|
Filipodia and lammelipodia
|
|
|
Which appendage is made up of actin gels?
|
Lammelipodia
|
|
|
Which appendage is made up of actin bundles?
|
Filipodia
|
|
|
What allows for actin treadmilling and what type of flow is this?
|
Removal of actin subunits from the - end and addition on the + end, retrograde flow
|
|
|
How are actin monomers organized? What filaments form what structures?
|
Monomers can form bundles, chains, or branch into networks
Branched monomers are found in lamellipodia and bunched monomers in filipodia |
|
|
What is the role of arp2/3?
|
Arp2/3 binds actin subunits to form a branch
|
|
|
How does mtubule treadmilling compare to actin treadmilling?
|
Mtubules cycle through rescue and catastrophe phases where subunits are added and constantly being lost
|
|
|
What is meant when we refer to mtubules as being dynamically unstable?
|
Tubulin subunits have low affinity in organized polymers and will continuously dissociate from the structure
|
|
|
What happens if you label and area of dynamic microtubules?
|
The area will not change, rescue and catastrophe occurs at a specific end of the mtubule
|
|
|
How does the clutch mechanism pair together with actin flow to produce forward growth?
|
When the clutch engages the macrostructure of the axon is pulled forwards along the direction of actin retrograde flow
|
|
|
What structures use the clutch mechanism in growth cones?
|
Filipodia
|
|
|
What are the stages of axon growth?
|
Protrusion, Engorgement, Consolidation
|
|
|
How does filipodial withdrawal and dilation work in tandem to direct growth cone around barriers
|
Filipodia near barriers withdraw and away barriers dilate to cause net movement around barriers when clutch engages
|
|
|
Can microtubule dynamics regulate axon turning?
|
Yes
|
|
|
What are Rho GTPases
|
molecular on switches with autophosphatases that turn themselves off (cleave Pi from GTP)
Causes collapse of growth cones when turned on |
|
|
What does cofilin do to actin turnover?
|
Cofilin promotes actin turnover, which causes the filaments to destabilize
|
|
|
What are 3 rho GTPases and what do they affect?
|
Rho - actin contraction
Rac - lammelopodia CDC42- filipodia |
|
|
Can growth cones find targets without a functional actin cytoskeleton?
|
No
|
|
|
What are two families of cell adhesion molecules?
|
Immunoglobulins and cadherins
|
|
|
What occurs when cx1 cell is ablated?
|
Axon growth ceases
|
|
|
What kind of environment do growth cones preferentially seek out?
|
Adhesive environments
|
|
|
What adhesion receptors can act as the clutch mechanism?
|
Integrins in the ECM
|
|
|
What is the alternate clutch mechanism and what does it stimulate?
|
Adhesion plaques, cause intracellular signalling through associated proteins
|
|
|
What is the purpose of the antibody neutralization assay?
|
To identify cell adhesion molecules
|
|
|
Within classes of adhesion molecules in the growth cone, which are Ca dependent? homophilic? heterophilic?
|
Cadherins are homophilic ca dependent
NCAMs are homophilic and heterophilic |
|
|
What is the role of beta catenin?
|
Recruits and organizes signalling and functional molecules in the intracellular domain of the adhesion molecule, engages the clutch/affects cell transcription
|
|
|
What are the phenotypes of L1 family mutants?
|
Deficient in somatosensory and spatial learning, guidance error of cerebellar axons
|
|
|
What are two ways L1 signals through pathways?
|
via the intracellular domain and via integrin activation
|
|
|
What is the structure of NCAM protein and how does it mediate adhesion?
|
Has many Ig like domains in a chain that regulate adhesion and fibronectin type 3 domains near the membrane
|
|
|
What happens when you treat NCAM with PSA?
|
Interactions between Ig Domains becomes limited to cross linkages and cis interactions are promoted, also affects BDNF to promote sensitivity to released growth factors
|
|
|
What changes occur in chick embryo innervation when treated with endo-N? How?
|
Nerve roots do not separate and remain in bundles, lack of spatial organization, axon targeting errors
Endo N removes sialic acid from NCAMs |
|
|
What are semaphorins?
|
A family of repulsive guidance molecules
|
|
|
Where is sema III expressed?
|
Ventral spinal cord
|
|
|
Does sema III repel NT3 dependent afferents?
|
No
|
|
|
Does sema III repel NGF dependent afferents?
|
Yes
|
|
|
What do semaphorins act as?
|
Morphogens
|
|
|
What are short range contact attraction cues?
|
Ig CAMs, Cadherins, ECM laminins
|
|
|
What are short range contact repulsion cues?
|
Eph ligands, semaphorins, ECM tenascins
|
|
|
What are two receptor types for semaphorins?
|
Neuropilin and plexin
|
|
|
What is the pathway for sema signalling?
|
sema binds neuropilin, plexin is activated to go through conformational change, frees GEF FARP2, turning on RAC1, activating RasGAP, turning off RAS, inactivating axons, growth cone collapses
|
|
|
What is FARP2? What happens when sema is not bound?
|
FARP2 modifies the sema receptor indirectly by turning on RAC1, does not effect outside of affecting the receptor's cofactors
|
|
|
What are commissural pathways and how does the chemoaffinity theory figure into the making of these pathways?
|
Pathways that cross the midline and then project along the midline, must be a combination of different chemoaffinity effects to create this structure
|
|
|
What are netrins? Where are they made/found?
|
Netrins are long distance chemoattractants that are made/found in the floor plate
|
|
|
Is netrin necessary and sufficient for pathway formation?
|
yes
|
|
|
What is the direction of trochlear motor axon growth with respect to the floorplate?
|
Away from the floor plate
|
|
|
What is DCC?
|
A netrin receptor required for attractive growth towards the floor plate
|
|
|
How is UNC5 used? What is its relation to DCC?
|
UNC5 is a netrin binding protein that modifies the DCC receptor mediated attraction into repulsion
|
|
|
Axons are attracted to the midline but grow past it, why?
|
Axons lose responsiveness to netrin after crossing the midline, netrin insensitivity means axon gives way to other chemical guides
|
|
|
What is slit and robo?
|
Slit is a secreted chemorepellent and Robo is its receptor
|
|
|
What induces the expression of robo?
|
Floor plate, so growth cones are only sensitive to slit after passing the floor plate
|
|
|
Why do axons grow towards the floor plate while slit is present?
|
Prior to reaching the floor plate, robo receptors that respond to slit are not expressed
|
|
|
What does ROBO activate?
|
Rho A rhoGtpase, also turns off CDC42
|
|
|
What are the effects of active ROCK protein?
|
growth cone collapse due to actin myosin interactions, stress fibre formation, cell contraction, and activation of cofilin
|
|
|
What is the cytoplasmic domain of ROBO needed for?
|
Slit mediated silencing of netrin sensitivity
|
|
|
What is an alternative way to block attraction via DCC?
|
Administer DCC binding antibodies
|
|
|
Is netrin a morphogen?
|
No
|
|
|
How do morphogens interact with axons to direct growth?
|
Wnt gradient is sufficient to redirect axons that have crossed the floor plate up its gradient
|
|
|
What are two long range cues?
|
Netrins and secreted semaphorins
|
|
|
What are some reasons that damage CNS neurons do not regenerate?
|
Intrinsically incapable of regeneration, lack the trophic factors needed, mature white matter inhibits regeneration, glial scars are physical barriers to regenerating axons
|
|
|
In Cajal's concept of terrain, what system is permissive for growth?
|
PNS
|
|
|
What are some differences in myelination between the nervous systems?
|
Schwann cells myelinate the PNS and one S cell makes up one myelin sheath
Oligodendrocytes myelinate in the CNS and make many sheaths for each O cell |
|
|
How does Wallerian degeneration contribute to axon regeneration?
|
Breakdown of myelin sheath, removal of cellular degree by macrophages, increase CAMs, neurotrophins, laminin, and premyelination
|
|
|
Can CNS neurons regenerate when transplanted to new terrain?
|
No intrinsically incapable of regeneration
|
|
|
What is the glial scar composed of?
|
Mass with abundance of ECM, damaged myelin, oligodendrocytes, meningeal cells, astrocytes, macrophages, and reactive progenitor cells
|
|
|
What 3 proteins in CNS myelin inhibit axon growth?
|
MAG myelin associated glycoprotein, OMgp myelin oligodendrocyte glycoprotein, Nogo A
|
|
|
Myelin inhibitors bind to which receptor to activate what pathway?
|
NgR (Nogo receptors) GPI linked protein receptors (no transmembrane domain) that activate RhoA/ROCK
|
|
|
What do GDI's do to this pathway?
|
Keep Rho A turned off
|
|
|
What chondroitin sulfate proteoglycans are found in glial scars?
|
NG2 and neurocan
|
|
|
What is their effect on regenerating axons?
|
Prevents regenerating axons from going through the glial scar by repelling them
|
|
|
What is a prerequisite for axonal regeneration after injury?
|
Formation of the growth cone
|
|
|
How does par-3 affect growth cone formation? |
Interacts with CDC42 and cofactors to form a polarity complex that promotes growth cone formation by turning on Rac |
|
|
What is the mechanism for NG2?
|
Induces hyperactivity of Rac1 to cause actin networking and collapse the growth cone
|
|
|
What is one way to rescue axon regeneration in vitro?
|
Administer chondroitinase ABC
|
|
|
What are proteoglycans?
|
Complex carbohydrate chains containing embedded proteins of the ECM
|
|
|
What silences netrin sensitivity?
|
Slit
|
|
|
What are opcs? |
OLIGODENDROCYTE PRECURSOR CELLS, PROGENITORS FOR OLIGODENDROCYTES AND CAN BE FOUND IN GLIAL SCAR |
|
|
What are some functions of glia |
Provide growth factors to modify axon growth, myelinate axons, regulate synapse formation, metabolize ntmitters, respond to injury, act as adult stem cells |
|
|
What occurs first, gliogenesis or neurogenesis? |
Neurogenesis precedes gliogenesis in the same progenitor cell |
|
|
What is gcm? |
Gene necessary for glial cell development in flies, affects the progenitor cell to make glia instead of neurons |
|
|
What is the mechanism and associated proteins of gcm? |
Creates tfactor ttk to silence neuronal differentiation Creates tfactor repo to induce glial differentiation |
|
|
What are some markers for opcs? Mature oligodendrocytes? |
NG2 and lack of MBP (myelin basic protein) Mature stops expressing NG2 and expresses MBP |
|
|
Which morphogen gradient domains generate oligodendrocytes and astrocytes? |
PMN and p2 domains after the development of motor neurons and v2 interneurons respectively |
|
|
What happens to olig2 -/- mice? |
No OPC generation |
|
|
Where do oligodendrocytes orginate? |
Ventral spinal cord |
|
|
Is shh needed for oligodendrocyte development? |
Yes, loss of function experiments show that oligodendrocytes fail to grow in the absence of shh |
|
|
What is the pathology of multiple sclerosis? |
Auto-immune mediated attack on oligodendrocytes which destroys the myelin sheath |
|
|
What are the four classifications of ms? |
Benign, relapsing/remitting, secondary chronic progressive, primary progressive |
|
|
How does the immune system facilitate demyelination? |
T-Cells are recruited to release pro inflammatory cytokines and TNFalpha which targets oligodendrocytes |
|
|
How does inflammation contribute to demyelination? |
Induces infiltration by phagocytes and inflammatory factors can induce apoptosis |
|
|
Why could remyelination fail in progressive ms? |
Failure of oligodendrocytes to repopulate the affected region, failure to differentiate, lack of trophic support from the axon |
|
|
Where are wnts found in spinal cord? |
Dorsally |
|
|
How does wnt signalling work? |
Wnt binds frizzled to stop degradation of beta-catenin |
|
|
How do wnts affect oligodendrocytes? Remyelination? |
Wnt inhibits oligodendrocyte development, delaying the differentiation of oligodendrocytes Beta catenin also found to delay remyelination |
|
|
What is active in demyelinating ms plaques? |
Wnt signalling in oligodendrocytes |
