Biology 441, Spring 2014


Summary Outline for First Exam

I am assuming that you will review the notes and study questions for the first three lectures:

Mammal embryo development in contrast to other vertebrates - look especially at the table for the January 8th lecture, and the figure (gastrulation.gif linked to the January 10th lecture)

Subdivision of embryos into germ layers. See the notes for January 13, and the first set of review questions.


The following are some additional notes to help you organize the material in the last few lectures:

Different kinds of symmetry (not just well-known mirror image symmetry and "radial symmetry")

Also rotational symmetry, displacement symmetry, dilation symmetry (magnification)

Hermann Weyl's definition of symmetry, as restated by Richard Feynman "If there is something you can do to it, and it looks the same when you get through"

So if you can find or invent some other, new "symmetry operation" (thing you can do to it) after which it looks the same, then that's a new kind of symmetry.

Two examples, important to crystallographers are glide reflection and inversion to a point. WWWWWWWWW has glide reflection symmetry.
If a crystal structure lacks inversion through a point, with respect to charged ions, then it will be piezoelectric.
Don't bother to memorize these two; you can probably figure them out, and learn more from the process of figuring.

Curie's law: effects have the same symmetries as their causes (and sometimes more) Most early embryos are spherical because their shape is caused by balances between spherically symmetrical forces (like osmotic pressure and surface tension)

How to "Break Symmetry" without becoming random is a big problem for embryos. Breaking symmetry can be accomplished either by getting external signals that have less symmetry (Examples: point of first sperm entry, direction of gravity, 9-fold rotational symmetry of flagellar basal body)

...or by processes like Turing's "Reaction Diffusion System" that magnify and selectively propagate random irregularities, in ways that can produce very regular displacement symmetry.

[Note: at least two quantitative variables are needed for such mechanisms, but they don't have to be chemical concentrations; they don't even need to be scalar variables. Also action at a distance does't have to be by diffusion, or spherically symmetrical.]

ALSO NOTE: Turing mechanisms can produce planes of reflection symmetry in spheres if they have short enough wave-lengths.

Scientists (including me) and mathematicians are just now getting around to inventing symmetry breaking mechanisms that * use different variables than chemical concentration (especially tensor variables). * use signals other than diffusion gradients, that have different ranges, instead of different diffusion rates. * break symmetries in addition to displacement symmetry. * Produce dilation symmetry (in the sense of reducing wave-length in proportion to smaller embryos.

To make discoveries in the direction, all you need to do is to write computer programs as simple as have shown in this class.

What physical forces shape embryos: PRESSURES: 1) Hydrostatic pressure (inside the brain, inside the eyeball, inside ducts, blood vessels and the heart. )

2) Osmotic pressure (inside cells; any place surrounded by continuous semi-permeable membranes)

3) Electro-osmotic pressure (sulfated gels) Cartilage is the main example. Does't need semipermeable membranes. (Resulting pressure can vary gradually from point to point, not just in jumps like osmotic pressure)

4) Growth; which can include mitosis, cytokinesis, enlargement of cell volumes, secretion of space-filling extracellular material. (Usually turns out to be really something else). Examples: skin thickening, elongation of hair & scales, tumor growth, & please think of other examples; there probably are some)

Notice that all 4 of these pressures are spherically symmetric, because caused by scalar variables. Therefore they can produce less symmetrical shapes only with the help of vector and/or tensor variables

5) Elastic tension for example in extracellular collagen fibers, and plant cell walls

6) Cytoplasmic acto-myosin contraction: To bend epithelial sheets; to contract epithelial sheets.

7) Actin treadmilling: to produce traction forces, by which animal cells crawl (and which also caused retrograde transport as a side effect)

8) Traction pulling collagen and other extracellular fibers relative to stationary cells, so as to realign collagen to form tendons, ligaments, dermis, organ capsules, and the tunica media (wall) of arteries and veins.

9) Work of Adhesion: As when water is pulled into a towel or kleenex by attraction forces that pull water toward wettable surfaces.

NOTE: Although work of adhesion definitely occurs in non-living systems, only some scientists believe that cells are pulled around the body by the process of forming new adhesions. That is the heart of Malcolm Steinberg's "Differential Adhesion Hypothesis" but many of its supporters do not realize what they are buying into.

Cells definitely use adhesions to pull themselves; but it is doubtful if the formation or enlargement of adhesions pulls cells.

Please invent some experiments that might be able to measure what fraction of cell propulsion is driven by work of adhesion.


Specifically Regarding Sorting-Out of Randomly Dissociated Cells

Discovered by H. V. Wilson, first using sponges, later using hydroids (and by others in some other invertebrates, including sea squirts)

Johannes Holtfreter demonstrated cell sorting in embryonic cells of frogs and salamanders. Ectoderm sorts out from mesoderm, neural tube ectoderm sorts out from skin ectoderm, and dozens of other combinations. Used color differences between species to prove that cells are rearranging and not dedifferentiating.

Hypothesized that sell sorting is caused by differences in tissue affinity. This idea stimulated searches for cell surface proteins that selectively adhere to each other; Many cadherins, N-CAM, and other selective cell-cell adhesion proteins got discovered. (an important conceptual breakthrough toward understanding how genes cause and control embryological shape formation)

John Phillip Trinkaus uses radioactive cell markers to prove that dissociated mammal and bird cells do not redifferentiate (which he had hoped to discover), but decides that whatever causes cell sorting can't be important in normal development, because eye cells sort out from leg cells, which they never normally touch.

Bond & Harris discover that sponge cells rearrange constantly, even when not dissociated. Richard Campbell and JoAnne Otto discover how Hydra cells bud be cell rearrangement, rather than growth or dedifferentiation.

Malcolm Steinberg proposes the Differential Adhesion Hypothesis, according to which maximization of adhesions (what he called "Reversible Work of Adhesion" is the driving force that causes cell sorting, independent of what kind of cell-cell adhesion protein occurs.

By measuring the resistance of cell aggregates, he believed he was measuring this hypothetical "Reversible Work of Adhesion", (See pages 70-75 in the tenth edition of Scott Gilbert's textbook, and other pages in other editions.

I have written papers claiming that he was really measuring the strength of active surface contraction of cell aggregates, and that "Reversible Work of Adhesion" doesn't exist for living cells & is a misunderstanding of Thermodynamics.

99% of embryologists think we are both crazy, & that cell sorting is not directly relevant to how embryos develop.

Those who believe that cell sorting is just something that happens, from which nothing can be learned about normal development:
Trinkaus, & probably most scientists

Those believing that cell sorting is caused by the same mechanisms as cause gastrulation, neurulation, and regeneration:
Holtfreter, Steinberg, Harris, maybe Dick Campbell?

But the important thing is to figure out what experiments could settle the issue; please do not feel pressed to believe either extreme.


Alternative Ideas why forces stabilize specific anatomical shapes:

Tensegrity: Advocated by Donald Ingber, Steve Levin (balances between pushes and pulls) (But why at certain shapes.)

Reversible Work of Adhesion: Advocated by Steinberg, and many collaborators. Thermodynamics somehow finds balance.

Shape Homeostasis: Advocated by Tim Otter, Albert Harris, and almost nobody else has even heard of it. Forces change shape in response to organs being the wrong shape, creating imbalances back toward stability

Notice that all three depend on stable balances between opposite forces. Only the third suggests how stability is made to occur only when certain geometrical shapes occur, and even it is extremely vague about how forces are made to vary with shape. Please invent more possibilities, or methods capable of DISproving these three.


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