Axon Guidance

Front 1

The Growth Cone

Back 1

respond to different chemicals sent by target cells like chemoattractants and chemorepellants

10-20 um in length, longer than cell body usually

-depending on its makeup can be inhibited or attracted to certain cues

Front 2

Epilepsy, autism, schizophrenia are primarily caused by defects in

Back 2

neural migration during weeks 12-20

Front 3

Attractive and repulsive cues to the growth cone

Back 3

Front 4

Netrin induces

Back 4

outgrowth. It is an attractant to the growth cone

Front 5

Semaphorins are

Back 5

repellents for the growth cone

Front 6

axonal guidance occurs ____. Why?

Back 6

Early; to simplify things. If you build up earlier, it's easier to modify later.

Front 7

Netrin is produced in

Back 7

the floorplate and ventricular plate to draw neurons down

Front 8

TF Netrin is always an attractant

Back 8

False, Netrin can function as a repellent thanks to molecular versatility

Unc5 receptors allow neurons to be repelle by netrin instead of attracted. The same situation occurs for other attractants/repellents with different receptor/ligand combinations

Front 9

How do a limited number of molecular cuessolve the wiring problem?

Back 9

1. Simplicity:

• start early

• use intermediate targets

2. Versatility:

• use multiple and redundant cues

• positive and negative

• permissive and instructive

• use cues that are multi-functional

3. Plasticity:

• allow errors early, refine later

• learn as you go (modulation of responses)

Front 10

Corpus callosum is formed by

Back 10

week 20

Front 11

How does neuronal wiring occur in stages?

Back 11

1) Extend axon ventrally

2) Grow towards floor plate

3) turn and grow towards brain

Netrin is secreted ventrally and causes growth in the direction, Shh induces turning

Front 12

Commissural neuron outgrowth

Back 12

Attractive protein cues cause them to extend from dorsal, cross over the midline into ventral and extend there.

Front 13

Axons grow towards the floor platebecause

Back 13

they are attracted to Netrin-1.

Front 14

Trochlear Motor Axonsgrow

Back 14

away from the floorplate (remember the trochlear nerve is the odd cranial nerve that doesn't come around ventral

Front 15

Netrin inhibits outgrowthof the (which cranial nerve)?

Back 15

Trochlear (4)

Front 16

after neurons cross the midline, netrin causes them to do what?

Back 16

Nothing, after neurons cross the midline, they stop responding to netrin

They are now repelled by slit

Front 17

Unc5 related receptors

Back 17

allow neurons to be repelled from netrin instead of attracted

Front 18

Roof plate produces

Back 18

BMP; repels axons

Front 19

Congenital Mirror Movement Disorder is a result

Back 19

hands move at the same time because there is no commnunication between hemispheres

Front 20

Plasticity is necessary for axons to

Back 20

leave the midline

Front 21

At what point do axons gain the ability to respond to other cues?

Back 21

When they reach the floorplate.

Commissural axons begin to express Robo and grow away from Slits that are expressed in the floorplate (at the midline).

Front 22

Explain how a commissural neuron grows in 3 steps

Back 22

Front 23

How do axons use several mechanismsto change their responses to cues

Back 23

1. Receptor interactions modulate signaling

2. Changes in the intrinsic state of the cell

3. Local protein synthesis or stabilization

Front 24

When the Robo3 receptor is present, axons

Back 24

ignore slits

Front 25

When Robo3 is absent or mutated, axons

Back 25

no longer enter the floorplate

Front 26

Horizontal Gaze Palsy with Progressive Scoliosis (HGPPS)

Back 26

Loss of horizontal saccades and/or pursuit in both eyes in lateral gaze.

Corticospinal and somatosensory tracks are uncrossed

Rig1/ROBO3 is mutated in HGPPS

Front 27

Slit2 _____ Netrin response

Back 27

silences

Front 28

Changes in the intrinsic state of the cell can be manifested how?

Back 28

cAMP levels affect how cells respond to ligands

Front 29

BDNF:

Back 29

normally attracts xenopus spinal cord neurons

Front 30

EphA2 is translated

Back 30

only after crossing themidline.

Controlled by specificsequences in the3’ UTR of EphA2

Front 31

How does axon guidance signalinglead to directed outgrowth?

Back 31

Front 32

Directed movement of the growth coneinvolves regulated changes in the cytoskeleton. What are they?

Back 32

Front 33

what regulates the cytoskeleton?

Back 33

Small GTPases

• Rho, Rac, Cdc42• well characterized regulatorsof the actin cytoskeleton• Regulated by binding GDP/GTP

• GAPs: inactivate (~80 in mammals)

• GEFs (Guanine Exchange Factors): activate (~70 in mammals)

Front 34

Chemoaffinity hypothesis

Back 34

Proposed by Roger Sperry that neurons or their axons and dendrites are drawn toward a signaling chemical that indicates the correct pathway.

Front 35

The Stripe Assay

Back 35

temporal axons of retina only want to grow on anterior tectum tissue but nasal axons grow regardless of anterior or posterior tectum tissue; happens because posterior tectum secretes repulsive signal (ephrin) and temporal axons are the only one to have receptor for signal

Front 36

Ephrin receptors are

Back 36

tyrosine kinases

Front 37

ephrin ligands are

Back 37

membrane bound repellents

Front 38

ephrin

Back 38

Cell surface tethered guidance cues. They react with Eph receptors in juxtacrine signaling (interact with other proteins on other cell surfaces). Ephrine in sclerotome extra-cellular matrix repels the migrating neural crest cells that have Eph receptors on their surface.

Front 39

Ephrins and their receptors generate

Back 39

generate topographic maps

Front 40

How does ephrin signaling cause temporal retinal neurons to know where they're going?

Back 40

Front 41

EphA and EphB signaling in the retinal pathway

Back 41

Front 42

How is a smooth map generatedusing Ephrins and Eph receptors?

Back 42

• Ephrins can be both attractive and repulsive.

• Ephrin activity is exquisitely concentration sensitive.

Front 43

increases in cGMP/cAMP levels cause? Decreases?

Back 43

Increase: usually attraction

decreases: usually repulsion

Front 44

EphA and B specify what?

Back 44

the lateral-medial axis

Front 45

What is fasiculation? What does it involve?

Back 45

the formation of a bundle of axons.

Involves adhesion molecules

-May have secondary effects on guidance and topography

- May also be used to follow pioneer axons

Front 46

TF Sema3A attracts axons and dendrites

Back 46

False, Sema3A repels axons, but DOES attract dendrites

Front 47

Dendritic tiling

Back 47

Dendrites must avoid themselves and other axons, so they repel through Dscam (Down Syndrome cell adhesion molecule)

Front 48

What kind of receptor is Dscam?

Back 48

a netrin receptor

Front 49

Dscam mediates

Back 49

self repulsion

Front 50

Give an overview o f how axons are guided to the right location

Back 50

Front 51

How does autism relate to axon guidance?

Back 51

Too many connections, too many spines. Improper growth.

Front 52

synkinesis

Back 52

movement disorders

Front 53

agenesis

Back 53

corpus callosum growing in the wrong way (not uniform)