Axon Growth Flashcards
Understand the basic mechanisms of axon growth and guidance during development Understand the main classes of molecules and pathways guiding axon growth during development
What makes neurons unique?
Their elongated morphology and their functional ability to be excited
Name the five essential components of axon growth
Extracellular guidance cues, growth cone receptors, intracellular signalling, cytoskeletal rearrangements, changes to nuclear transcription
Which molecule controls retrograde transport along axon microtubules?
Dynein
Which is the major molecule controlling anterograde transport along axons?
Kinesin
Why do axons contain mRNA in their axoplasm and growth cones?
To allow local transcription to occur fat from the nucleus, to satisfy demands fr protein synthesis at distant sites
Which second messenger group controls actin assembly and disassembly?
The Rho GTPases
What underlies growth cone dynamics?
Cytoskeletal changes in actin filaments and microtubules, controlled by intracellular signalling
Name the most important pathway in actin assembly and disassembly
The conversion of Rho-A, Rho-B, or Rho-C into ROCK
Describe the Wnt family
The Wnt family is a large family of secreted molecules that stimulate synaptic differentiation by modulating microtubule dynamics in the growth cone
Describe the action of neurexin
Neurexin stimulates pre-synaptic differentiation by binding to cell surface neurexin on the incoming cell
Name two positive long-range guidance cues
Neurotrophins, e.g. nerve growth factor, and netrin
Name the netrin receptor expressed by commissural neurons in the dorsal spinal cord
Deleted in colorectal cancer (DCC)
Which receptor must neurons express to respond positively to nerve growth factor (NGF)?
TrkA
Name three growth factors which bind to the TrkB receptor
Brain derived neurotrophic factor (BDNF), neurotrophin 4, and neurotrophin 5
Which receptor must neurons express to respond positively to neurotrophin 3?
TrkC
Which inhibitory receptor do all neurotrophins bind to?
p75
Why do up to 50% of neurons die without innervating their target?
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
Which cells express cell-associated short range axon growth cues?
Neurons, astrocytes, oligodendrocytes, and Schwann cells
NCAM is a short-range axon growth cue. Name five functions it is involved in
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
Name the two short-range cell-associated axon guidance cue superfamilies
The immunoglobulin superfamily and the cadherin superfamily
Name two extracellular matrix associated short-range growth cues
Laminin and collagen
Name the major growth cone receptors for extracellular matrix molecules
Beta 1 integrins
Describe the role laminin plays in optic nerve development
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
Name a common beta 1 integrin binding motif
RGD motif, found in extracellular matric molecules
Which molecule is essential for TrkA transport?
APP, an important protein for fast anterograde axonal transport
Which disease can be modelled by NGF antibody expressing mice?
Alzheimer’s disease
Name three negative soluble long-range guidance molecules
Netrin, the semaphorins (e.g. semaphorin III), and slit
Which cells secrete slit?
Midline cells
Which receptor combination causes netrin to become repulsive, and how?
DCC and Unc55
The combination decreases cyclic AMP, and increases calcium ion concentration and cyclic GMP
Which receptor does slit act on?
Robo receptor
Which molecule removes Robo receptors from the growth cone?
Commissureless (Com)
Name two classes of short-range repulsive axon guidance cues
Ephrins and membrane-tethered semaphorins
Name three extracellular-matrix associated repulsive axon guidance cues
S-laminin, tenascin, and chondroitin sulphate proteoglycan
What is the difference between type A and type B ephrins?
Type A are GPI-anchored, whereas type B are transmembrane
What are Eph receptors?
Tyrosine kinase receptors which activate Rho GTPases to stimulate growth cone collapse. There are two classes - EphA and EphB - which respond to ephrins
What controls the formation of the topographical map of the retina in the visual cortex?
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
