Module 1 Lecture 5: Target Selection Flashcards
topographic map
ordered projection of a sensory surface (eg skin or retina) or an effector system (eg musculature) to regions in the CNS
defining feature of topographic maps
neighbor relations in the sensory surface are preserved in target area
where does optic topographic mapping occur
back of retina, superior colliculus, tectum, lateral geniculate nucleus, visual cortex
chemoaffinity hypothesis
2+ cytochemical gradients in the retina and tectum stamp the RGCs and target with matching chemical codes (identity) to establish the observed mapping
roger sperry’s experiment
- cut the optic nerve of an amphibian
- rotate the eyeball 180 degrees
- wait for regeneration
- assay for visual behavior
result of roger sperry’s experiment
animals behave as if their world is turned around
- never learn
where does the nasal retina map to
posterior tectum
where does posterior retina map to
anterior tectum
what causes topographic mapping between the retina and the tectum
built-in, anatomical features, rather than experience
first step of Bonhoeffer’s experiment
prepare cell membrane from anterior and posterior tectum (chick)
second step of Bonhoeffer’s experiment
deposit membrane in very thin alternating stripes
third step of Bonhoeffer’s experiment
test how retinal axons across the nasal temporal axis grow on stripes
fourth step of Bonhoeffer’s experiment
treat posterior membranes with protease or PI-PLC (phsphatidylinositol-specific phospholipase C), which cleaves PI
results of Bonhoeffer’s experiment
- nasal axons have no preference
- temporal axons prefer anterior membrane
- preference lost with membrane treatments; consistent with repulsive influence from posterior membranes
conclusion fo Bonhoeffer’s experiment
glycosylphosphatidylinositol (GPI)-linked cell surface protein enriched in the posterior tectum triggered repulsion of temporal axons
what does ephrin-5A do
causes growth cone collapse
where is ephrin-5A found
enriched in the posterior tectum
two types of ephrins
- ephrin-A: GPI linked
- ephrin-B: transmembrane domain
- 8 ephrins in mammals
- As bind As, Bs bind Bs
what are ephs
receptor tyrosine kinases; important to cell proliferation and survival, as well as migration and axon guidance
what kind of signaling do ephrins do
- forward signaling (ephrin:Eph)
- reverse signaling (Eph:ephrin, the ephrin expressing cell responds)
- bidirectional signaling: both cells respond
what is the gradient in the tectum
posterior to anterior high-to-low ephrin-A5 and -A2
what is the gradient in the retina
temporal to nasal high-to-low EphAs
how does the posterior tectum affect axons from the temporal retina
repelled
relationship between temporal retina axons and the posterior tectum with ephrin-A2, A5 double mutants
they can target the posterior tectum
if topographic mapping is based on repulsion, then how do nasal axons avoid the anterior tectum?
counter gradients and reverse signaling:
- tectum: A-to-P high-to-low EphAs
- retina: N-to-T high-to-low ephrin-A5
- axons from nasal retina are repelled from anterior tectum due to ephrin reverse signaling
what system guides the axon maps from the retina to the superior colliculus and the dorsal lateral geniculate nucleus, from the dorsal lateral geniculate nucleus to visual cortex, and visual cortex back to the previous stuff?
EphA and ephrin-A counter gradients
do counter gradients of EphB and ephrinBs exist, and what do they do?
yes, exist alongside non-graded expression in the D-V axis of the retina and the medial-lateral axis of the superior colliculus
what do Cajal-Retzius cells express
multiple Eph receptors and ephrin ligands
wildtype Cajal Retzius cells vs EphB1/B2/B3 triple mutants
wildtype cells display contact dependent repulsion; EphB1/B2/B3 triple mutants cluster
what is required for wildtype Cajal-Retzius cell distribution
contact-dependent repulsion
hypotheses for why the CNS is built up in layers
- protect info –> minimize entropy
- minimize energy
what happens if Robo2 is mutated
RGC axons spread across depth of tectum; some project to multiple layers and have diffuse terminal processes
what happens if Slit is knocked down
same as if Robo2 is mutated
what happens if Slit is overexpressed
same as if Robo2 is mutated
what happens if Collagen IV is mutated
no Slit and RGCs looks same as if Robo2 is mutated
where does Slit protein accumulate
in the basement membrane, under the skin cells
- stays there by sticking to Collagen IV
steps for development of retina
- optic vesicles extend from neural tube
- turn into cups (now two layers)
- overlying ectoderm thicken and invaginates; will become the lens
where does most computation occur in the retina, and what types
inner plexiform layer
- visual features such as light on/off, edges, colors, direction of motion
where does the vertebrate retina originate from
pseudostratified neuroepithelium
- retinal progenitor cells (RPCs) are connected to both apical and basal laminae and divide preferentially at the apical domain
is the retina built inside-out?
no
recoverin function
marks photoreceptors
what kinds of gradients of development exist in the retina
spatial, in addition to temporal
- central retina develops ahead of peripheral retina
how do bipolar cells target to the OPL and IPL
by retracting the apical and basal processes of retinal progenitors
where do bipolar dendrites form
at the BPL
where do bipolar axons form
at the IPL
order of addition to IPL
- amacrine cells (2nd born)
- retinal ganglion cells (1st born)
- bipolar cells (last born)
where do tyrosine hydroxylase (TH) - expressing dopaminergic amacrine cells predominantly stratify
within the S1 sublamina of the IPL in wild-type
where are Sema5A and 5B expressed
in the developing mouse outer nucleoblast layer (ONBL)
what happens in Sema 5B and 5A/5B mutants
dopaminergic amacrine neurons, which normally have projections in the S1 layer of the IPL, mis-target into the INL
where do melanopsin expressing intrinsically photosensitive RGCs predominantly stratify
in the S1 sublamina of the IPL in wild-type
what is the working model of targeting to the IPL
- during early retinal development, class 5 semaphorins are expressed by cells in the ONL
- contact with Sema5-expressing tissues biases the extension of neurites, such as those of tyrosine hydroxylase-expressing dopaminergic amacrine cells (DACs, ‘TH’)
- following initial redirection, DAC neurites extend into the OFF layers of the IPL
characteristics of PlexinA4 and Sema6A proteins
expressed in a complementary pattern in the developing inner plexiform laeyr
ipRGCs and DACs relationship
synaptic partners (make synapses together)
what happens in PlexA4 mutants
both ipRGCs and DACs extend far deeper into the IPL
- new extensions appear to overlap
what happens in Sema6A mutants
same as in PlexA4 mutants
what cells express PlexA4
DACs, not ipRGCs
Sema6A functioning in deeper layers of the IPL
keeps PlexA4 expressing DAC processes confined to the S1 layer
characteristic of ipRGC targeting
may be dependent on its direct interactions with DAC processes
class 5 semaphorins function
direct the neurites of DACS (‘TH’) to the IPL
ipRGC (‘M1’) targeting to the S1 layer of the IPL characteristic
may be guided by its interactions with DACs
examples of homophilic binders
Cntn2,3,4, Sdk1, Sdk2, Dscam, DscamL
- do not interact with each other
what does RNAi-mediated knockdown of Cntn2 cause
disruption of Skd1 expression layer
CAM-code model of IPL layer targeting
each synaptic lamina has a unique combination of homophilic cell adhesion molecules, encoded by related genes of the immunoglobin superfamily
- misexpression and knockdown experiments show that these cell adhesion molecules can be sufficient and necessary for targeting synaptic terminals to specific sublaminae
what does ONL stand for
outer nuclear layer
what does OPL stand for
outer plexiform layer
what does INL stand for
inner nuclear layer
what does IPL stand for
inner plexiform layer
what does GCL stand for
ganglion cell layer
