Lecture Notes for April 24, 2019

Future Medical Applications of Embryological Phenomena:

If only we understood just a little more about certain subjects, many, lives could be saved.
Let's consider examples.

#1) Bone formation:
What do osteocytes do
that causes bone to crystallize next to them?

Possibility #1: (Secrete calcium ions and/or phosphate ions at concentrations larger than the solubility product of calcium phosphate?)

Possibility #2: (Secrete extracellular matrix proteins that somehow decrease solubility of calcium phosphate?)

How do increased mechanical stresses cause increased bone formation?
Conversely, how do weightlessness and older age decrease bone strength?

Is it really true that electrical fields, created by bone stress, increase bone?
Are the electrical fields caused by the piezoelectric effect,
or have researchers been misinterpreting electroosmosis?

Shouldn't it have been relatively easy to solve all these questions?

What is the obstacle? Lack of Imagination?
Are the answers too complicated for our minds?
Do we lack certain knowledge, or certain experimental methods?

If you could ask Santa Claus for some specific knowledge, what would it be?

We don't even know what additional knowledge we need most!




#2) Atherosclerosis:

Why do smooth muscle cells and macrophages accumulate among the cells of the walls of arteries, especially downstream of turbulence and where pressure is greatest? Do these cells crawl there? How much mitosis of these cells occurs? How much do these cells rearrange?

If it were simply a matter of cholesterol and cells sticking to the insides of blood vessel walls, then wouldn't more "plaque" stick to the insides of veins?

These are life and death questions for tens of millions: How can they go unanswered?




#3) The theory proposed by David Stopak and me:

What process builds skeletal muscles, wraps organs and arteries with collagen, etc.?


Our evidence: Time lapse videos of mesenchymal cells on cartilage surfaces rearranging collagen and muscle cells to form realistic skeletal muscles.

video of cells aligning
This is a series of time-lapse clips photographed using polarized light. As collagen is aligned, it shows up as bright spots or aligned structures.





Other evidence: The demonstration by scientists at Charles University in Prague (also called Universität Carolinensis) that non-living surgical "sponges" can get attached to frog skeletons and aligned where the gastrocnemius should be.

Counter-evidence: mutant mice with weakened traction still form normal-looking muscles, although their wound closure is much slower than normal.

Bruce Carlson and some other people think we have misinterpreted wound-closure mechanisms as being the methods of embryonic structure building.

How could these debates be settled?
If either we or our critics could discover how hundreds of alternating perpendicular layers of collagen, form our cornea, tongue, and notochord sheath.




My paper recently written and published in honor of the great Russian embryologist Lev Beloussov, who died a year and a half ago.
link to this paper online
Photocopies (reduced in size to save paper) were also handed out in class.

How can physical properties of cells cause their geometric shapes?

Using homeostasis to try to explain tube formation.

If being cylindrical is sufficient to cause strengths of circumferential tension to exert twice the force of longitudinal tensions, then is the reverse also true?

Is having a two to one ratio of directional tension enough to cause surfaces to become cylinders? (Just as having surface tensions be equally strong in all directions causes materials to round up into spheres.)