Second set of review questions for the third hour exam

"Chemotaxis" is the name given to any case in which cells or neural axons are guided toward targets by gradients of concentrations of any chemical.

Describe three possible mechanism that can produce chemotaxis.
*Maybe you can invent a fourth. * Would you use this same word ("chemotaxis") to describe any means of accumulating cells at locations where some chemical's concentration is higher than elsewhere?

Which kind of chemotaxis is used by bacteria? By white blood cells? By Dictyostelium amoebae? By ciliate protozoa? By nerve growth cones of the ganglion cells, as they form the optic nerve by crawling out of the retina, under the brain, up the side of the midbrain, and connecting to the optic tectum to create a neural projection.

Do nerve fibers from the eye innervate the brain (optic tectum)?
Or do nerve fibers from the brain innervate the eye? (actually, some do.)

How are ephrin proteins and ephrin receptor proteins believed to participate in the formation of the neural projection? *In what sense is it "repulsion" for a chemical to induce detachment of cells? *Would less strongly contractile cells be less strongly "repelled" by stimulation of detachment? Would larger cells be repelled at longer distances? Or at least seem to be?

Ephrin proteins have been found to have locally increased concentrations in the boundary areas where somitomeres are splitting apart into separate somites: Explain why this helps explain segmentation of vertebrate bodies.
Hint: by inducing cell-cell detachment

* Steve Roth demonstrated that more cells from dorsal halves of chicken retinas will stick to ventral halves of chicken mid-brains ("optic tectums") [the real plural of tectum is tecta . Second declension neuter. Which you don't need to know]
This greater accumulation was interpreted as evidence that each part of the retina is more adhesive to the part of the tectum that it innervates. * Would that evidence have convinced you? *Would it have occurred to you that the real cause would be greater stimulation of detachment in the areas not innervated?

* Symmetry? Does less detachment equal more adhesion? … Less adhesion = more detachment? More pressure = less pulling; etc. Experimentally, can one distinguish whether any given phenomenon is caused by more of one variable, as opposed to less of its opposite? (Not an easy question; and not just "semantic".)

*The next time you learn that a given phenomenon is caused by maximization of "X" will you try to invent a symmetrical reverse-explanation based on minimization of whatever is the reverse of X? (If X plus Y = constant. then maximization of X equals minimization of Y? Are these the same? *Or are they just difficult to tell apart? Can you think of some examples of this kind of similarity of double-opposites, either from embryology, biology, or any other field?
This question is not without interest; would you not disagree?

Suppose cells can measure or compare concentrations of a substance on different parts of their surface, how should they change the direction of their locomotion in order for chemotaxis to occur?
There are several possibilities:

    What if they turn toward their side where the detect the highest concentration of the chemical?

    What if they continue crawling in the same direction as long as the chemical concentration increases, but then turn if and when the chemical concentration decreases?

    What if they continue in a direction as long as the chemical concentration at their front end is higher than elsewhere,but turn if the concentration becomes higher on any other part of their surface?

* By what angle should they turn in order to achieve chemotaxis? (trick question)

* By what angle should they turn in order to optimize chemotaxis? (In the sense of reaching their target soonest, and after moving the minimum average distance?)

What if cells continue crawling, with random turns, as long as the concentration of a certain chemical is between a certain minimum and a certain maximum, and stop if the concentration gets above this maximum, and reverse direction if the concentration is below the minimum?

    Would you classify this as chemotaxis?
    Could you distinguish this from chemotaxis, if you watched cells behaving this way?

    Could this process serve the normal functions of chemotaxis?
    For leucocytes?
    For nerve growth cones?
    For future egg and sperm cells finding the future testis and ovary? For sperm cells finding egg cells?
    For muscle cells finding their correct site of attachment to bones?
    For capillaries vascularizing tissues which are not yet receiving enough oxygen?
    For the pronephric duct finding its correct path from the pronephros to the cloaca?
    For the ureter connecting to the metanephros?
    For the oviduct connecting to the vicinity of the ovary?
    For optic nerve fibers to find their way toward the blind spot?

How is chemotaxis used by leucocytes to home in on wounds and locations of infection?

Could endothelial cells use chemotaxis to vascularize tissues in an optimal pattern? (get enough oxygen everywhere with the minimal total length of capillary?

Could sensory and motor nerves use chemotaxis to guide them toward connection to the proper locations in the skin, or on muscles?

What difficulties can you think of, for using this guidance mechanism? (I can think of at least two big ones.)


When your eye detects light, in what sequence do light rays reach the following structures and differentiated cell types: (Please arrange in the correct order)
*Ganglion cells; *Pigmented retinal cells; *Cornea; *Rod and Cone cells; *Lens; *Optic nerve fibers

Why do vertebrate eyes have"blind spots" (In terms of the sequences of embryonic cell folding and cell crawling?)

What is a neural projection?
What are three examples of neural projections?
skin - central nervous system>
muscle - central nervous system

Which of these has been subject to the most intensive research?

Most nerve fibers from the right eye connect primarily to what part of the brain? (In chicken, frog, and fish embryos. It's a little different in mammals)

What are ephrin proteins?

Where are these proteins found to occur in concentration gradients?

What are ephrin receptor proteins?

In what cells are amounts of ephrin receptor proteins found to occur as a concentration gradient?

* Why do we need to have at least two different kinds of ephrins, each specific for binding to its own kind of ephrin receptor?
two-dimensional projections

In what directions to the gradients of ephrins and ephrin receptors need to vary, relative to each other, in order to cause optic nerves to project in the actual geometric patters that they do project?
Draw a diagram of this.

What experiment did Steve Roth and his collaborators do in an attempt to discover the mechanism of formation of the retino-tectal projections?

What was his experiment designed to detect? What mechanism of nerve guidance did his experiment assume was most likely to be true? To what extent was Roth correct? To what extent was he not correct?

What results did he get, that seemed to confirm his hypothesis?

Figure out and explain what really must have been happening in Roth's experiments.

Why did these results seem to confirm Roth's favorite theory, even though it was not correct?

* Could computer simulations have helped Roth?

When people say that binding of ephrin to ephrin receptors "repels" cells from each other, what do they really mean?

In this metaphorical sense of the idea of repulsion of nerve growth cones, which nerves will be most strongly repelled by cells with any given amount of ephrin receptors?

For any given growth cone of the optic nerve, which cells of the optic tectum will "repel" it most strongly?

* Argue pro or con, whether you would regard these effects as either chemotaxis or haptotaxis?

*Do you think optic nerve cells and optic tectum cells continue to have ephrin and ephrin receptor gradients all during life, at least in salamanders?
hint: if they can regenerate eye-brain connections

Experiments were done grafting pieces of retina to the surface of the tectum: What result do you suppose the experimenters hoped (expected) to observe?

Why didn't they get any consistent pattern of connection, resembling a projection, do you suppose?

*Can you invent some other experiments that scientists should have tried?

What pattern of connection is formed when two eyeballs (and two optic nerves) are forced to innervate the same side of the brain?

In principle, what OTHER patterns of connection might have developed, instead?

* Suppose you had invented the theory that ganglion cells sent out growth cones at a sequence of specific times, and that these were 'attracted" chemotactically to one side of the tectum, with the ganglion cell growth cones competing with each other for connections to locations on the tectum,"first come first served", with each nerve fiber forming a permanent connection, blocking other optic nerve fibers from connecting there, and being blocked from connecting to other locations where other optic nerves had already connected.

    1) Could this timing mechanism, in principle, create a neural projection?
    2) Which experiments (Roth, double eye grafting, eye rotation, etc.) would have produced different results that they actually did produce, if retina-tectal projections really had been produced by this hypothetical timing mechanism?
    3) Are there some results that would have been the same?

What is interesting about the paths of optic nerve fibers in the optic chiasm? Can you explain this pattern by ephrins and ephrin receptors?

In species of animals that have stereo vision, what happens to some of the nerve growth cones in the optic tectum (that is different from what the other optic nerve fibers do)?

* What could be the mechanism of this?

* Why do you suppose that those nerve fibers that turn back to the same side of the brain wait until they have gone all the way to the chiasm before turning 90 degrees?

In fact, half retinas spread out over the whole tectum. Would you have expected that? What does it tell you about causal mechanisms?