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Developmental Neurobiology 🧠 > Exam 2: Chapter 5 > Flashcards

Exam 2: Chapter 5 Flashcards

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1
Q

Axon growth occurs from the

A

growth cone

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2
Q

How do axons find targets?

A

Mechanical and chemical cues

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3
Q

Growth cones use ___ to changes shape

A

mobilization of cytoskeletal proteins

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4
Q

Short distance

A

interneurons

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5
Q

Long distance

A

projection neurons

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6
Q

Challenges faced by early axons

A

find their own path

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7
Q

Challenges faced by late axons

A

traverse complex environment

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8
Q

Zebrafish: look at axons, what happens

A

16-36 hr, nothing to a lot, real quick and efficiently

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9
Q

Grasshopper Ti Cells

A

axons use guidepost cells. If you ablate the guidepost cells, they lose their way

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10
Q

Hibbards Mauthner neurons

A

rotated salamander hindbrain 180 degrees
Normal: cross midline and go caudal
Rotate Soma 180: go rostral, but then hit the barrier and go back (little loop)

Significance: External cues too, not just intrinsic program

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11
Q

What happens if you cut through a frog tectum as it develops, cutting axon from soma?

A

still grows for a while, but won’t get to target

Significance: growth cone sufficient for environment response

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12
Q

What is faster: early or late axons?

A

Late, they have a path to follow

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13
Q

Growth cone shape depends on

A

filopodia

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14
Q

Growth cone speed (optic tract –> Tectum)

A

Slows down when it gets to the target (slows for tectum)

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15
Q

Growth cone at target

A

flattens and collapses

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16
Q

Pioneer (leader) axons

A

active filopodia
few lamellipodia
elaborate growth cones

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17
Q

Follower axons

A

simple, bullet shaped, few filopodia

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18
Q

Growth cones are complex at

A

midline

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19
Q

What happens at growth cone midline crossing?

A

Leaders become followers

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20
Q

Time lapse imaging

A

Method using GFP gene: make own floursecent protein, shows axons en route tectum. Watch growth in tissue

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21
Q

How do growth cones elongate?

A

Material added distally, Ca2+ dependent.

At actin/microtubules at axon tips

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22
Q

Experiment: FRAP fluorescence with bleach

A

bleach is still as growth cone advances, suggest distal assembly. If it had moved, then it would be soma.

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23
Q

Experiment: beads on axons, actin in axons

A

Beads: some interstitial growth, they move apart a little

Actin: at tips, goes back into the axon

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24
Q

P-zone

A

periphery, actin

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25
C-zone
Central zone, microtubues
26
___ tethers actin/microtubules to use for transport
myosin
27
Growth Cone Guidence needs ___ and ___ interaction
filopodia and microtubules
28
Cytochalasin
inhibits filopodia formation | actin depolymerizing agent
29
Cytochalasin Experiment
Control: axon to tectum Cytochalasin treated: can't find tectum Significance: actin filaments critical for growth cone navigation
30
How does 1 filopodia move growth cone?
Tension Myosin pulls actin cables: clutch release mechanism disconnected tubulin pulled forward actin added at + end, disassembled at - end.
31
Axon turns in direction of polymerization and stabilization, as experimentally shown with
taxol
32
Axon turns away from depolymerization as experimentally shown with
cytochalasin and nocodazole
33
1) Mechanical Guidance
Physical Aspects of environment | Follows grooves/physical terrain
34
Mechanical Guidance experiment
cut corpus C. Can guide around aspar region blocking Artificial sling can get to other side
35
2) Adhesive Guidance (CAMS)
Filopodia adherence
36
Adhesive stuff
L1, polylysine
37
Non Adhesive stuff
cadherin, laminin, plain glass, plastic
38
Shape of growth cone on adhesive stuff
flat, slow growth cone
39
Shape/speed of growth cone on less adhesive stuff
fluffy and fast
40
Is adhesion enough? Sometimes. What is the systems
Less adhesion: fast Adhesion: where you wanna go, it's a balance test for it by blasting air, see if it will detact
41
Homologous
Cadherin/Some CAM
42
Heterologous
Some CAM/Integrins
43
CAM heterophilic example
TAG-1 in interneurons binds to NrCAM in glial floorplate
44
CAMs
big protein, membrane bound, gives neurons preferences
45
Cadherins
Ca2+ dependent, need exact match
46
Integrins
Alpha/Beta subunits | connect to other stuff like ECM, Fibronectin, and Laminin
47
Vertebrate CNS adhesive path vs. PNS
CNS: laminin (retinal axons like it) PNS: fibronectin
48
Chemotaxis
Molecules attract and repulse
49
Examples of chemoattraction
Nerve growth factor (NGF)
50
Example of Chemorepulsion
Semaphorin
51
Drosophilia Fas2
bundles axons together. Fas2 in CAM, sticks together KO Fas2- wandering axons increase Fas2- stick too long Significance: on and off selectively
52
LAMP- CAM in limbic system
needed for limbic connections, if LAMP antibodies in mouse brain, abnormal fiber projection. Enhances neurite outgrowth 3x IgG domains
53
Neural Cell Adhesion Molecules (NCAM)
Some internal domains | Extracellular modified by carb residues, reduce adhesion
54
Nonsialyated with sialic acid
Very adhesive (less is more)
55
Sialyated
not adhesive
56
Sialic acids controls
defasiculation of certain nerve pathways Polysailaic acid = less sticky CAM
57
Experiment: Endo-N, what does it do?
Digests sialic acid to make things more sticky
58
Labelled Pathway in the Grasshopper: What happens if P axons ablated?
G can't follow P anteriorly. Need P-axons before G crosses midline. Axons have specific molecules on surface, lay down pathways which help other neurons find their way
59
Sometimes need to change CAM on surface
``` CNS: longitudinal tract (Fas2 homolog) Horizontal commissure (Fas1) Allows midline crossing ``` Looks like a ladder. CAM tells where to cross
60
Chemorepulsion: what does the semaphoring family do
Repulse DRG neurons to allow targeting DRG neurons want dorsal Collapsin is a semaphoring, shown to repulse growth cone Semaphorin in ventral to keep DRG away
61
Experiment: DRG and dorsal and ventral tissue
DRG goes dorsal
62
Experiment: Olfactory and Septum
Olfactory grows away from septum
63
Experiment: DRG and notochord and dermomytune
DRG grows in between them
64
Vertebrates: KO Semaphorin
overgrowth in projections from both motor and sensory nerves --> peripheral targets
65
What determines if a molecule is attractive/repulsive?
2nd messengers
66
Local Cue test: 1) remove tectum 2) rotate epithelium square
1) still grow towards it 2) correct once they exit the rotated piece Significance: local cues matter
67
Ligand/Receptor: Neterin (unc-6)
Receptors: DCC (Unc-40 in C. Elegans) Attractive
68
L/R: Slit
Receptors: | Robo = repulsive
69
L/R: Wnt
Receptor: Frazzeled = attractive Ryk = repulsive
70
Wnt is pro-
Anterior
71
Experiment: add cos cells with wnt in wrong place
grow posteriorly instead of anteriorly
72
Experiment: Ko Frazzeled receptors
not A or P after crossing
73
If it's anterior commissural interneurons, what wnt receptors?
Frazzeled
74
If it's posterior descending neuron, what wnt receptor?
Ryk
75
Netrin location
Netrin/Unc-6: midline | Netrin-1: floorplate
76
Experiment: Unc-6 mutant
growth defect
77
Experiment: Unc-40 mutant
Can't orient
78
Experiment: Netrin-1 KO
Dorsal commissural interneurons can't get to ventral midline
79
In vertebrates, DCC gets axons to ____-
Floorplate
80
Slit is a ligand found in
ventral midline
81
Olfactory bulb and motor neurons have ___ receptor
Robo, repulsive
82
Experiment: fuse robo and frazzeled
attracted to slit, repelled by netrin intra Fraz + Extra Robo Intracellular domain = attraction driver
83
Experiment: 1) Commissurless mutant 2) Roundabout mutant
1) no Comm to destroy Robo before crossing, so it never crosses 2) only crosses, nothing to stop robo from crossing Slit at midline.
84
Drosophila Axon midline crossing
DCC-netrin gets axon to across | Once netrin leaves, slit sensitive, barrier up
85
Vertebrate midline crossing: | Types of Robos
Rig 1 = Robo 3 = Comm Robo 3A = against Robo Robo1/Robo 3B - repulsive, regular Robo
86
Vertebrate midline crossing: Before crossing
Robo 3A is high , so inhibits Robo1 Meanwhile, Netrin --> DCC, so attraction
87
Vertebrate midline crossing: After crossing
Robo 3B is high | Slit binds to Robo 1, which inhibits DCC and causes repulsion
88
If its in a vertebrate, and never meant to cross
no Robo3A
89
KO misexpress Robo in vertebrates
Shifts intermediate to medial and vis versa
90
Drosophila Experiment: 1) normal motor neuron (AVM) with Unc-40 2) Unc-40 and Unc-5 3) Unc-6 Mutant with any Unc-40/5 combo
1) Goes ventral 2) Goes dorsal 3) no preference Why? unc-5 hates netrin even though unc-40 loves it. Also: downstream signaling (cAMP levels) Netrin + DCC = more cAMP, actin polymerizaition, attraction Low cAMP = depolymerization, now repulsive
91
Retina --> Tectum Pathway
1) Laminin: force axon in certain direction, low cAMP so repulsive, causes turn for netrin 2) Slit/Shh repulsive, but leaves chaism as pathway for dorsal/nasal axon to cross. Slit is guiding RGC. 3) Ephrin-B attracts to midline 4) Sema3A- repulses to tectum 5) decrease in FGF to show destination reached 6) Gradient of eph/ephrin/wnt = where to plug in
92
Axons vs. Dendrites: Semaphorin
Axon- repelled (white matter) Apical Dendrite: attracted +cGMP = Sema attractive now
93
If you cut axon process on developing neuron
another minor process will replace if done early enough
94
Axon proteins
viral HA, HaemR1-distal, GAP43, Tau
95
Dendrite Proteins
GluR1, HA with GLuR1 C-terminal Tag, HaemR1 and HaemR1-proximal, MAP2

Developmental Neurobiology 🧠 (11 decks)

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