Development 2 Flashcards
4 main stages of development
neural tube + crest formation
AND generation of neurones
neurone migration
projection of axons to targets
synapse formation + excess neurone death
2 groups of molecule involved in axon guidance + synapse formation
adhesion molecules
guidance cues
synapse formation
- when?
- what does this allow?
- what happens if a neurone doesn’t connect with target?
when axons reach their targets
neurone survival
apoptosis of neurone
synapse formation
- in muscle cells
= neuromuscular junctions
even after junctions are made, some are eliminated until each muscle fibre is innervated by only 1 motor neurone
selection of correct connections
apoptosis eliminates inappropriate connections
growth factors secreted by target cells keep the neurone alive
- excess neurones die
target cells also die
- could be neurones with target dependency competing for GFs
topographic projections
- what is it?
within each target there’s faded innveration for finer control or to provide more info
topographic projections
- examples
mapping of medial-lateral axis of neurones from spinal cord to single muscle across dorsal-ventral axis e.g. gluteal muscle
mapping of retinal axis across axis of target nucleus in brain (tectum in birds)
= allows speck use of vision
switch in dependence
axons most reach target and form connection before neurones become dependent on target cells
factors in pathway to target cells
secreted from glia or other cells in pathway :
adhesion molecules
guidance cues
target switching in brain development
some neurones must innervate a secondary target before reaching primary target
so transitory dependence on a secondary target
- > innervation of primary target
- > pruning/complete loss of innervation of secondary target
haptotaxis
- define
= directional outgrowth of cells due to adhesive gradients
CAMs
cell adhesion molecules
expressed by growth cones
-> modulate adhesion to ECM + other cells
recognise same molecules (homodimers) or different types of AM
can be adhesive or prevent growth
adhesive molecules
- examples
CAMs
= recognise basal lamina proteins
laminin
= direct axonal tracts
(even if only transiently)
glycosaminoglycans
= impeded neural outgrowths
CAMs
- examples with location + role
Ig-Cam + NCAM
- around cell membrane + bind molecules in membranes of neighbouring cells
Integrins
- sit in cell membrane + bind molecules in ECM
Cadherins
- localised to specific junctions + bind proteins in similar junctions on neighbours
cadherins
- features
links to actin cytoskeleton via catenins
Ca2+ dependent
transmembrane
homophilic
Ig-CAMs
(immunoglobulin- CAMs)
- features
links to actin cytoskeleton
Ca2+ independent
IgG domains bind to similar domains on other cells
transmembrane or surface-bound
integrins
- features
links to actin cytoskeleton
Ca2+ dependent
transmembrane
binds to glycoproteins in ECM
axonal fasciculation
- define
growing axon adhering to another
forms axon bundle groups
example of contact attraction
axonal fasciculation
- maintained by
cell adhesion keep axon groups together
nerve branching
- define
- why does this occur?
axons divergence when following different guidance cues
molecules in environment that affect cell adhesion
- > NCAM polysialylation
- > regulates homophilic interactions
which molecule group is involved in axon pathfinding?
guidance cues
axonal growth cone
- mediation of movement
mediated by cytoskeleton lacttice containing actin + myosin
axonal growth cone movement
- filopodia
made of actin + detects environment
polymerisation extends filopodia towards guidance molecule
de-polymerisation of actin when guidance cue repels
axonal growth cone
- structure
lamellipodia + filopodia
has CAMs + receptors for guidance cues
axonal growth cone movement
- neurite
neurite extends behind moving growth cone
-> microtubule backbone of neurone constructed from tubular molecules
growth cones respond when they bind guidance cues
- features of guidance cues
contact-mediated and chemotropic
attractive or repulsive
act over short or long range
can differentially affect different neurones
how does the growth cone move through tissues?
secretes proteases
-> break down ECM of cells
GAP-43
allows us to identify growth cones
unknown function
2 agents that inhibit normal growth cone activity
cytochalasin
- binds to monomeric actin
- > block it from polymerisation
phalloidin
- binds to polymeric actin
- > blocks actin breakdown
using phalloidin + cytochalasin in an experiment
have 2 growth cones
apply potential guidance cue
apply phalloidin to one
if nothing happens
-> sign of repulsion
(cytochalasin -> sign of attraction)
