Lecture 7 - Development Flashcards
What are the three main hypotheses for how axons find their targets and which one was found too be correct?
- mechanical guidance (steriotropism) - growing axons follow a track
- resonance - growing axons induce the identity of their partners the postsynaptic cell (axons from the presynaptic cell creates a target and whatever it synapses with will develop an identity based on the presynaptic cell
- chemoaffinity - growing axons use chemical cues pre and post synaptic cells have ligand/receptor pair (this is the correct hypothesis)
What was Roger Sperry’s classic experiment?
-used frogs and wanted to see how axons regenerate and whether he can measure behavior which in this case is fly catching
-in the experiment he crushed the optic nerve (regenerates in frogs)
-rotated the eye 180 degrees
What were the findings of Roger Sperry’s classic experiment and what were the two possibilities which could happen?
Possibility #1: ganglion cells would grow and connect to a new target appropriate to their new locations and the frog will behave normally
Possibility #2: ganglion cells will grow back to their original target based on their original location in the eye and the frog will see everything rotate up = down and forward=backward
Result - the ganglion cells grow back to their original target because the frogs stick their tongue out when the fly is behind it and cannot catch the fly
In Roger Sperry’s classic experiment, how did the sensory axons grow back to their original target?
-originally the temporal retina projects to the anterior tetchy and the nasal retina projects to the posterior tectum
-the posterior tectum is wired for you to stick you tongue out so when the eye is rotate the projections are still the same but the frog cannot stick tongue out
-since after rotation by 180 degrees the former temporal still projects to the anterior tectum and the former nasal still projects to the posterior tectum
What are the different types guidance cues?
attraction - short range and long range
-repulsion - short range and long range
What experiment was conducted in regards to short range guidance cues, the results, and the conclusion made?
-retinal ganglion cells were grown on tectal membranes painted in stripes on a dish
Results - 1. temporal retinal axons grow only in the anterior tectal membrane
2. nasal axons grow on both
Conclusion - there is a short range interaction between the axons from the temporal retina and proteins in the tectal membrane
-temporal neurons could be attracted to the anterior tectum or repulsed by the posterior tectum
What experiment was conducted to determine whether temporal neurons could be attracted to the anterior tectum or repulsed by the posterior tectum, what were the results, and the conclusion?
Experiment - boil extracts of tectal membranes from either the anterior or posterior retina to inactivate biological activity
Results - no effect of heating the anterior membrane and inactivating it they still grew straight
2. heat inactivation of posterior membrane disrupts the preferred of temporal axons
Conclusion - the active component is in the posterior membrane and it is repulsive and prevents the temporal axons from projecting there
What was the short range repulsive guidance cue that was discovered to be secreted by the posterior tectum to repel the temporal axons from projecting there and what two experiment were done to prove it?
ephrin
Experiment 1 - over expression of ephrin - temporal axons avoid high regions of ephrin
Experiment 2 - ephrin KO - the temporal axons project to the posterior tectum
What kind of guidance cue is collagen and why?
short range attractive since neurons like to stick to it and grow where it is present
In short range attraction what is the mechanism of action?
there are many different types of adhesion molecules similar to collagen and they generally work by physically connecting two membranes like a zipper
In the chick spinal cord where to commissural neurons project to?
the bottom of the spinal cord known as the floor plate
What was believed to attract commissural neurons to the floor plate of the chick spinal cord and what experiment was run?
long distance cues
Experiment: isolated the active component from extract of the floor plate that induces the growth fo the roof plate to the floor plate
-the molecule identified was netrin
-netrin is a long range attractive cue (Sanskrit for one who guides)
What was found in the study that generated a netrin KO?
the axon projections from the dorsal to ventral spinal cord were disrupted
What was found when there was a cell type specific KO of netrin in floorplate cells?
there was no affect of the projection of axons from the roof plate to the floor plate
What was found when there was a cell type specific KO of netrin in ventricular zone or middle and what does this prove?
the projections were in fact disrupted; netrin instead might power axon movement and instead is not a long range attractive cue since it might just function as a source to get the axons to keep traveling to their target but not function as a long range attractive cue
What is the netrin receptor?
DCC
What is the the receptor for the long range repulsion molecule slit?
Robo
What is slit?
a long range repulsion molecule
Can netrin also mediate repulsion and how?
yes it can; via the DCC/UNC5 receptor complex
What was found in the limb bud ablation and supernumerary limb bud experiments on chick embryos?
Limb bud ablation - ablated has fewer motor neurons and internal control has lots of motor neurons
Supernumerary limb bud - motor neurons overproduce on the added limb bud side
Conclusion - limb bud has a trophic factor or survival factor
What is a sex difference in neural circuitry (mice hamsters) between men and women and how did it come to be?
men have spinal nucleus of the bulbocavernous while women do not because testosterone is not active in women to act on the muscles which control the penis which causes a loss of neurons in the spinal nucleus of the bulbocavernous
