Sample review questions for third exam:

Sketch the shapes, arrangements and relative sizes of chondrocytes in articular cartilages.

Sketch the shapes, arrangements and relative sizes of chondrocytes near parts of bones where bone formation is occurring.

If all the calcium phosphate is dissolved out of a bone, what sort of thing is left?

    A brittle object the same size and shape of the original bone?
    A flexible, rubbery object the same size and shape of the original bone?
    A shrunken object, smaller but otherwise the same shape as the original bone?
    An inflated, larger object, bigger, but approximately the same shape of the original bone?
    Something else? What?
    The result cannot be predicted?
If all the collagen were somehow digested or otherwise removed from a bone, which of the listed results should occur?

If all or many of the sulfate groups were somehow digested or otherwise removed from a CARTILAGE, which of the listed results should occur?

If all or most of the collagen were somehow digested or otherwise removed from a CARTILAGE, which of the listed results should occur?
(If in doubt, explain your reasoning.)

How could any of these 4 changes in bones or cartilages (maybe) be of medical use?

Given the fact that electro-osmotic pressure is a scalar variable, and that the elasticity of collagen networks is a fourth order tensor, which do you suppose causes the shaping of cartilages and bones? Please explain your reasoning.
(The answer isn't quite as simple as you might guess).

Look at the changes in sizes and shapes of chondrocytes near where ossification is occurring.
Which of the following could provide the directional driving force that elongates growing leg bones, arm bones, and ribs? (Based on what you know about electro-osmosis; based on what you can see about cell shapes, sizes and arrangements?)

    * The chondrocytes orient their mitotic divisions, so that these will push in the longitudinal direction?
    * The chondrocytes secrete more sulfonated sugar chains from those sides of the chondrocytes that face the directions of elongation?
    * The chondrocytes cause digestion of sulfonated sugar chains in the DIRECTIONS of elongation?
    * The chondrocytes cause digestion of sulfonated sugar chains in the LOCATIONS closest to where new bone is forming?
    * The chondrocytes cause digestion of collagen fibers that resist osmotic swelling of cartilage?
?? Which of these explanations are taught in medical schools? Which are asserted on 99% of informational web sites about endochondral ossification? ? Which of these explanations are logically possible?
What experiments can you invent to prove or disprove each of these theories?

* Can you invent some additional theories to explain how bones "grow" in length? When you inflate a long balloon, does it grow?
Do nerve fibers grow? (Partly yes, partly no.) Please explain.

Do capillaries and other blood vessels GROW? (Partly yes, partly no.) Please explain.

Do cartilages GROW in length or width? (Partly yes, partly no.) Please explain.

Do bones GROW in length or width? (Partly yes, partly no.) Please explain.

Are the shapes of cartilages necessarily the result of more growth in some directions and/or locations? (Partly yes, partly no.) Please explain.


How is cell locomotion related to the paths of axons and dendrites in the nervous system?

Sensory nerve cell bodies are located where?

Motor nerve cell bodies are located where?

Postganglionic autonomic nerve cell bodies are located where?

Optic nerve cell bodies are located where? And are called by what name?

What physical process creates the wiring patterns (of nerve connections) inside the brain?

How was this discovered, and who discovered it? (Hint: Read the Wikipedia article on "tissue culture." But ignore what they say Roux; his tissues merely survived.)

What is chemotaxis?

What is haptotaxis? *Who discovered the phenomenon and invented the name? (Stephen Carter)
*Who discovered the mechanism? (i.e. why tissue cells move up gradients of adhesiveness?

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 optic projections?

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?

To what proteins do do ephrin receptor proteins bind specifically?

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?

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?

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 Wolpert says that binding of ephrin to ephrin receptors "repels" cells from each other, what does he 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?

* Would you regard these effects as either chemotaxis or haptotaxis?

* Would an optic nerve be able to form a correct pattern of connection if it entered the tectum at the wrong location? Why or why not?

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?

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 ephins 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?


Suppose that a row of cells varies in some quantitatively variable property (like amount of some protein on their surfaces); and also suppose that each cell can detect the amount of this quantity on its immediately neighboring cells as well as detecting its own amount of this substance.
Furthermore, suppose that each cell will change its own quantity to make it closer to the average value of its neighbors, how could this behavior of cells be used to create concentration gradients?

(That would look like diffusion gradients! But could be produced in variable properties that can't diffuse?)

You can experiment writing a row of ten random numbers on a piece of paper, then putting zero at one end and ten at the other end of the row. Then use a hand calculator or lap-top application to recalculate all the numbers in your row (averaging and changing, over and over again) writing newly calculated rows of numbers down your page.

If you don't let the end numbers change, then how many recalculations does it take to produce a gradient?

What are some anatomical patterns that can be helped by such a mechanism of repeated averaging? What advantage does such averaging and recalculation have, as compared with diffusion of a chemical "morphogen"?

Will this method produce gradients just as well for shorter rows of numbers (0, then 5 random numbers, then 10)?
What about for longer rows of numbers (0, then 20 random numbers, then 10).

Will it work for creating regular sequences of qualitative variables (differences in kind, instead of amount)?
(Hint: If each variation in the variable possesses some rule about comparing properties between neighbors, and how to change properties based on properties of neighbors.

Try alphabetizing exam papers. Put the exam by student Z at one end of a long table, and then put all the other papers in a random sequence. Alternatively just make a random stack of papers.
Then go down your row, or through your stack, one paper at a time, and if the names of the students of two adjacent papers happen to start with the same letter, then you don't move them. But every time adjacent papers are by students whose names start with different letters, then you rearrange them so that the one with the name that starts with the letter that comes later in the alphabet is put lower in the stack, or moved toward the Z end of the table - and you keep doing this over and over, you will eventually alphabetize the list.

Now think about the spatial patterns of Hox-genes! The geometrical pattern of their transcription in developing embryos! And think about what a big deal it would be if you could discover (meaning INVENT, TEST and PROVE) the mechanism that causes co-linearity.

Wolpert & nearly everyone expect the answer to be that some diffusible "morphogen" with low-enough molecular weight, and/or hydrophobic enough to diffuse through plasma membranes (retinoic acid? shh protein? something) forms a diffusion gradient from one end of each embryo to the other, and then the promotor regions of each hox gene detects the concentration of the morphogen, & decides whether to transcribe its mRNA or not, depending on the local concentration go retinoic acid, or whatever diffusible chemical.

Consider, instead, that cells might be able to detect which how genes are being transcribed by their neighboring cells, and change which how genes they express based on which are being expressed by their neighboring cells.

* What does the word "principles" mean, in the title of the textbook we are using?

Regulation of spatial patterns imply causation by gradients? Gradients are caused by diffusion?

To what degree are these plausible hypotheses, that might be true, but also might not?

Remember Roth's experiment. Notice how cartilage "growth" and shape are usually explained.


When do limb buds become irreversibly committed to their anterior-posterior "axis" (asymmetry), their dorso-ventral axis ( asymmetry) and their media-lateral axis?

By what experimental method were these facts determined in the 1920s and 1930s?

Describe the shape and location of the apical ectodermal ridge.

What happens to leg, arm or wing development if the apical ectodermal ridge is surgically removed early in embryonic development?
(Hint, what happens differs, depending on how early in development this thickening in the epithelium is removed)

* Salamanders are the only kind of vertebrate that can regenerate their legs, even after total amputation, and they are also the only kind of vertebrate that does NOT have an apical ectodermal ridge during embryonic development. (not counting snakes! which don't form limb buds at all)
Try to invent a hypothesis to make sense of this fact (not AER, but much better regeneration by salamander legs), and/or suggest medical uses of this hypothesis, if it turned out to be true.

What happens in limb development if tissue is grafted from just behind the limb bud to just in front of the limb bud?

By what surgical operation can a leg or wing bud be caused to branch and produce the equivalent of three hands?

By what surgical operation did John Saunders cause chicken wing buds to graft into four wing tips, instead of three?

In what sense is the triple branching of a reversed limb bud analogous to ordinary would healing and regeneration?
(Hint: remember what I said about cells responding to being surgically moved to a location adjacent to other tissues that they are not normally in contact with?)

* Can you think of some way to make sense of the quadruple branching of chicken wing tips, that John Saunders produced?
You will impress me very favorably if you can! So please think about this for a few minutes, with your fresh, unbiased minds.

What is programmed cell death? (Also called "apoptosis")

What are some specific examples of programmed cell death? (at least three)

What is the main molecular cause of programmed cell death?

What strange effects does retinoic acid have on limb bud symmetry?

What effect does retinoic acid have on limb bud regeneration?

What (really strange!) effect does retinoic acid have on tail regeneration?

What does it mean to say that retinoic acid is a teratogen?

What hypotheses are being made if someone concludes that retinoic acid is a morphogen?

Why would you expect any morphogen to be a teratogen, at least at some stage of development?

This completes the list of review questions.


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