Axon Growth

Question 1

What makes neurons unique?

Answer 1

Their elongated morphology and their functional ability to be excited

Question 2

Name the five essential components of axon growth

Answer 2

Extracellular guidance cues, growth cone receptors, intracellular signalling, cytoskeletal rearrangements, changes to nuclear transcription

Question 3

Which molecule controls retrograde transport along axon microtubules?

Answer 3

Dynein

Question 4

Which is the major molecule controlling anterograde transport along axons?

Answer 4

Kinesin

Question 5

Why do axons contain mRNA in their axoplasm and growth cones?

Answer 5

To allow local transcription to occur fat from the nucleus, to satisfy demands fr protein synthesis at distant sites

Question 6

Which second messenger group controls actin assembly and disassembly?

Answer 6

The Rho GTPases

Question 7

What underlies growth cone dynamics?

Answer 7

Cytoskeletal changes in actin filaments and microtubules, controlled by intracellular signalling

Question 8

Name the most important pathway in actin assembly and disassembly

Answer 8

The conversion of Rho-A, Rho-B, or Rho-C into ROCK

Question 9

Describe the Wnt family

Answer 9

The Wnt family is a large family of secreted molecules that stimulate synaptic differentiation by modulating microtubule dynamics in the growth cone

Question 10

Describe the action of neurexin

Answer 10

Neurexin stimulates pre-synaptic differentiation by binding to cell surface neurexin on the incoming cell

Question 11

Name two positive long-range guidance cues

Answer 11

Neurotrophins, e.g. nerve growth factor, and netrin

Question 12

Name the netrin receptor expressed by commissural neurons in the dorsal spinal cord

Answer 12

Deleted in colorectal cancer (DCC)

Question 13

Which receptor must neurons express to respond positively to nerve growth factor (NGF)?

Answer 13

TrkA

Question 14

Name three growth factors which bind to the TrkB receptor

Answer 14

Brain derived neurotrophic factor (BDNF), neurotrophin 4, and neurotrophin 5

Question 15

Which receptor must neurons express to respond positively to neurotrophin 3?

Answer 15

TrkC

Question 16

Which inhibitory receptor do all neurotrophins bind to?

Answer 16

p75

Question 17

Why do up to 50% of neurons die without innervating their target?

Answer 17

Neurons are programmed to die by apoptosis unless they are rescued by stimulation of a cell survival signal - e.g. a growth factor binding to their Trk receptor

Question 18

Which cells express cell-associated short range axon growth cues?

Answer 18

Neurons, astrocytes, oligodendrocytes, and Schwann cells

Question 19

NCAM is a short-range axon growth cue. Name five functions it is involved in

Answer 19

Inside CNS: Learning and memory, synapse remodelling, axon outgrowth, cell migration, cell-cell adhesion
Outside CNS: Pancreatic tumours, small cell lung carcinoma, natural killer cells, hair growth

Question 20

Name the two short-range cell-associated axon guidance cue superfamilies

Answer 20

The immunoglobulin superfamily and the cadherin superfamily

Question 21

Name two extracellular matrix associated short-range growth cues

Answer 21

Laminin and collagen

Question 22

Name the major growth cone receptors for extracellular matrix molecules

Answer 22

Beta 1 integrins

Question 23

Describe the role laminin plays in optic nerve development

Answer 23

Retinal ganglion cells navigate from the retina to the optic tectum along a pathway of laminin laid down by astrocytic end feet on the path of the optic nerve

Question 24

Name a common beta 1 integrin binding motif

Answer 24

RGD motif, found in extracellular matric molecules

Question 25

Which molecule is essential for TrkA transport?

Answer 25

APP, an important protein for fast anterograde axonal transport

Question 26

Which disease can be modelled by NGF antibody expressing mice?

Answer 26

Alzheimer’s disease

Question 27

Name three negative soluble long-range guidance molecules

Answer 27

Netrin, the semaphorins (e.g. semaphorin III), and slit

Question 28

Which cells secrete slit?

Answer 28

Midline cells

Question 29

Which receptor combination causes netrin to become repulsive, and how?

Answer 29

DCC and Unc55

The combination decreases cyclic AMP, and increases calcium ion concentration and cyclic GMP

Question 30

Which receptor does slit act on?

Answer 30

Robo receptor

Question 31

Which molecule removes Robo receptors from the growth cone?

Answer 31

Commissureless (Com)

Question 32

Name two classes of short-range repulsive axon guidance cues

Answer 32

Ephrins and membrane-tethered semaphorins

Question 33

Name three extracellular-matrix associated repulsive axon guidance cues

Answer 33

S-laminin, tenascin, and chondroitin sulphate proteoglycan

Question 34

What is the difference between type A and type B ephrins?

Answer 34

Type A are GPI-anchored, whereas type B are transmembrane

Question 35

What are Eph receptors?

Answer 35

Tyrosine kinase receptors which activate Rho GTPases to stimulate growth cone collapse. There are two classes - EphA and EphB - which respond to ephrins

Question 36

What controls the formation of the topographical map of the retina in the visual cortex?

Answer 36

Gradients of ephrin expression in the optic tectum and differences in the expression of Eph receptors in retinal ganglion cells. Ephrin A expression is low in the anterior tectum but high in the posterior tectum. Temporal retinal ganglion cells express many EphA receptors, while nasal retinal ganglion cells express few. The low levels of ephrin A in the anterior tectum can stimulate growth cone collapse in the temporal retina but not the nasal retina with fewer receptors. This requires the higher levels of the posterior tectum