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74 Cards in this Set
- Front
- Back
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Why is axon guidance an important phenomenon to study today? |
Genetic mapping correlate with important neurological diseases are related to axon guidance. |
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What is a very important difference between the CNS of an amphibian and a mamal? |
Regeneration is possible in the amphibian CNS but not for the mamal's CNS |
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Roger Sperry did what kind of experiment on a frog? What happened with it ? |
He could completely transect the optic nerve of an amphibian and observe a complete functional regeneration of it. |
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If the nervous system would follow a random outgrowth, what would be its profile? |
It would have no pre-determined specific axon guidance, would have a lot of incorrect targeting and would have an activity dependent correct targeting. |
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What would be the principle behind chemoaffinity based development ? |
Axons would follow specific molecular tags expressed by specific cells. |
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What evidence supports the chemoaffinity hypotesis? |
1Neurons are intrinsically different from on another 2Differences in position are biochemical in nature 3Differences are acquired early on in development |
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Briefly describe the anatomy of the visual system |
light comes in and hit the retina where retinal ganglion cells will convey information in the optic nerve, optic chiasm, optic tract LGN optic radiation into the calcarine sulcus. |
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What is the difference in axonal pathways in teh optic chiasm for amphibians and mamals? |
Amphibians: axon goes on the contralateral side Mammals: goes on both sides |
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Where to temporal RGC project to in the tectum and where do nasal RGC project to? |
Temporal: Anterior Nasal : posterior |
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Where to dorsal RGC project to in the tectum and where do ventral RGC project to? |
Dorsal: Ventral tectum Ventral: Dorsal tectum |
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How is the retinal image with respect to the world? How is the tectal image? |
Retianal : inverted tectal: uprigh |
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How can you assess if the axon guidance is random or defined? |
Cut the optic nerve and rotate the eye 180 degrees. and wait for regeneration. Chemoaffinity predicts a completly inverted visual field would be produced. |
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You cut the optic nerve of a tadpool and invert its eye and allow for regeneration. To your surprise, you have found no invertion effect. Is this evidence for a random based axonal guidance mechanism and why? |
No, there is the notion of a critical period where the system can adapt to the eye invertion. |
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The nervous system is composed of billions of different synapses following chemoaffinity direction. but you do not have as many genes. how do you acheive this variability? |
Using other factors such as combination, timing and positioning |
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IN what fashion do axons find theru targets?
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In a series of descrete steps
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Would all cell's axon repspond to the same queue in the same way?
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NO they will vary in their response.
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What is a growth cone?
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An enlargement at the end of an axon.
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What is the name referring to the actin rich finger-like parts of the growth cone?
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filapodia
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What is the name referring to the actin rich sheet-like parts of the growth cone?
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Lamellipodia
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What does the growth cone core contain?
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Microtubles, mitochondria and various vescicles
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What primarily mediates the extension of the growth cone?
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Actin polimerization
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What happens to a growth cone when it is in a cytochalasin medium?
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It will not grow at all (inhibits axon polymerisation)
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What are the three domains of the growth cone? What technique allows to differenciate them?
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Central transition and peripheral : can be seen using interference light microsocopy
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You observe a growth cone put in cytochalasin for 80 sec what will you see? Once cytochalasin is removed what will you see? This suggests what?
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Exposure: Actin filament will retract to the core of the growth cone Cease of exposure: will first find actin regrow forward: indicates the most active zone.
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Briefly explains how the growth cone advance
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Filopodium contracts an adhesion cue and contracts pulling the growth cone. Actin filament assemble at the leading edge. Exocytosis adds membrane to the leading edge to supply with new adhesion molecules
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What mediates the growth cone collapse internally ? What happens if you have asymetric collapse?
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F-actin retraction - asymetric will cause a steering of the growth cone
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What do repulsive and attractive cues directly affect in a growth cone?
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The rate of actin polimerization at the plus and minus end.
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What are 6 possible ways of directing axon growth?
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1: Growth promoting molecules 2: Adhesive cell surface growth 3: Axon fasciculation 4: attractive cue 5: repellant cue on surface of cell 6: repulsive cue
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Describe an experimental apparatus for studying the effets of extracellular matrix on axons
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Take an extracellular matrix extract and put it on a dish. Put a metal pattern and shine uv light : it will destroy the EM that is not covered by the metal. Whatch the axons grow
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What is the major factor in eth Extra cellular matrix which influences axon growth? What cell receptor interacts with it ?
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Laminin and integrins will interact with laminin.
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With which intra cellular components does integrins interact with?
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Alpha actin actinin and talin which pairs adhesion with cytoskeletal change for appropriate migration
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Describe an experimental apparatus to study the cell adhesion molecules in a neuron. |
Neurons are put in a solution: when swirled gently they often aggregate. Using an antibody specific to a cell surface molecule, you may stop the aggregation. |
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What are the two broad categories for CAMs? what is characteristic for each of them? |
Calcium dependent CAMs Immuniglobulin superfamily ( calcium independent and has a lot of Ig domains) |
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Give an example for both Calcium dependent CAM and immunoglobulin superfamilly molecules. |
N-cadherin and NCAM respectively |
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Name three extracellular matric molecules |
Chollagen Laminin Fibronectin |
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What defines the specificity of an integrin receptor? |
It is a dimer of an alpha and Beta subunit which has many subtypes different combinations will define specificity |
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What is the relevance of laminin in the visual system? |
Laminin is found in the retina which directs the axons of the RGC to the optic nerve. |
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When cell addhesion molecules bind together, what are the two possible types of binding that can occur? |
Homophilic and Heterophilic |
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What experimental apparatus defined the characterisation of Ephrines? |
Extract RGC from the anterior and posterior retina. Also extracted the tectum and created columns of alternating posterior and anterior regions. put the RGC in series and observed growth. Posterior RGC only grew on anterior tectum region while anterior RGC grew everywhere. |
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What are the two classes of ephrines and what characterises them? |
Epherine A and Epherine B A: no intracellular domain hence requires coreceptor for signaling B: has intracellullar domain |
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What are the two types of ephrine receptors? What kind of receptor activity will these receptor have? |
Eph A and Eph B. These receptor have tyrosin kinase activity. |
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What two kind of signaling can occur with ephrin and eph interaction. What can you presume about one of the two types of signaling? |
FOrward ephrine-eph (activity) ( receptor has activity) Reverse: (activity)ephrine-eph(activity) (ligand induces activity) Presumable reverse activity can only occur with Ephrine Bs. |
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What is the type of ephrine signaling in the tectum? |
Forward inhibitory signaling |
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How does epherine signaling explains the posterior anterior patterning of the tectum? |
tectum has a low to high epherine A5 gradient from the anterior to posterior part of the visual system. Posteriro RGC have a high concentration of EphA making them sensitiv to epherine A5 while anterior RGC have a low EphA concentration making them insensitive to epherine A5. Being repulsive Epherine A5 will create the patterning |
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What is the Epherine B1 profile with the tectum and ephB2 profile in the retina? |
You have an increasing gradient from ventral to dorsal in the tectum for epherine B1 while in the retina it is inverted. being an attractive each go to the corresponding concentrations. forward positive signaling |
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Are semaphorins repulsive or attractive cues? |
They are repulsive. |
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How can you identify a semaphorin? |
They have a sema domain |
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What is the difference between SEMA3 and SEMA4 |
SEMA3 is secreted and SEMA4 is tranmembrane |
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What does a cell require for it to be sensitive to Semaphorins? |
Requires both neurophellin and plexin. |
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If you clip the intracellular domain of neuropellin, what will happen to the cell with regards to its sensitivity to semaphorins? |
nothing |
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What compound prevent RGC axons from leaving the optic nerve? |
Sema5A in its surroundings |
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What creates the semaphorin signaling ? |
Nueropellin and plexin dimerises and induces a confirmational change which allow plexin to signal. |
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Where does the name Robo come from? |
THe round about phenotype when robo is KO |
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What factor is especialy important for crossing the midline ? |
Slit and its receptor Robo |
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Is slit a repulsive cue or attractant ? |
Slit is a repulsive cue. |
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When dorsal cells extend their axons towars the ventral part of the spinal cord, they intially are attracted but then repulsed once crossed the midline. What mechanism mediates this? |
The axon do not express ROBO initially. Slit is in high concentration in the midline and hence when axon crosses midline it start expressing robo which render him repulsed by slit. |
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What compounds ensure that the axons in the optic nerve crosses the optic chiasm? |
Slit 1 and 2 |
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What is the typical profile of axons of commisural neurons? |
They do from dorsal to ventral, cross mid line and go anteriorly (longitudinally). |
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Exlplain the experimental set up which led to netrin discovery |
Dorsal extract was put to a petry dish. beside it a ventral extract was put. Commisural neurons would grow toward the ventral region. |
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What are the two receptors to Netrin |
DCC and Unc5 |
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A growth an express both DCC and Unc5. WHat will be its response to netrin? |
It will be repelled by netrin. |
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A growth cone express DCC only. What will be its reponse to netrin? |
It will be attracted by it. |
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What factors on the dorsal region will repuls commisural axons? |
BMP and Draxin |
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What are the 3 main GTPases family members? |
RAC/DCD42 and ROW |
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What does Rac corellation relate to ? |
Lamelipodia formation |
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What does CDC42 relate to ? |
filapodia formation |
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What does Row formation will relate to ? |
Growth cone collapse. |
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Based on ROW RAC and CDC42 function, what will a semaphorin and what will a netrin with a neuronhaving only a DCC receptor activate in terms of gtpases ? |
Sema: ROW Netrin: CDC42 and Rac |
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What will mediate GTPase activity and what two factors will perform this modulating function |
Phosphorilation and dephosphorilation of GTP/GDP. GEFS will activate through GTP insert while GAPS will inactivate through GDP insert. |
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WHat does GDI do to GTPases? |
Will inhibit them |
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Ephexin can activate what of the GTPase family. when does each presumably occurs? |
Rho DCD42 and a little Rac. Rho: when bound to ephrine A ( ephA) rho kinase acivated When phosphorilated and bind other protein and bound to attractor: activate CDC42. |
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Based on GTPase activity, what is the current model of SLit robo activity? |
Slit binds robo which then activates a GAP for CDC42 limiting lameliipodia formation. |
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What would be the general pathway for guidance cue when taking in consideration the Gtpases? |
Cue- receptor ligand complex- activation of GEF GAPs of GDI-> activation of GTPase specific factor-> cytoskeletal change. |
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WHat determines the sign of the response to netrin intracellularly ? |
The ratio of cAMP/cGMP in teh cell will determine its response to netrin |
