What causes the asymmetry in a symmetrically developing organism?

[DaveC426913]

TL;DR

To put a fine point on it: why are our hearts always on the left and our ascending colons always on the right?

As child, before I got my first X-ray, I used to fantasize that I might have a mirror image anatomy - my heart on the right, my appendix on the right. Why not?

(Caveat: I'm not talking about sci-fi molecular-level mirroring. We're not talking starvation because I couldn't process certain proteins, etc.) I'm simpy tlakng about, when a normal zygote divides, it technically has two options which way to form. Oen would expcet a 50:50 split.

But we all have our heart on the left and our appendix on the right (with the exception of congenital deformities).

It's certainly understandable why we have asymmetry. The small intestine, for example is 20 feet long - it must make complex folds to fit into our abdominal cavity, and therefore must become asymmetrical. A more obvious example of aysmmetry is that the stomach's fundus is on left and the pylorus on the right.

The question I have is: why does the asymmetry always happen the same way? There's clearly a lot evolutionary development leading up to the complexity that is any macrofauna such as a human. Witpu doubt, the aysmmetry will become fixed very early in the foetal development.

But how exactly?

A single cell is symmetrical. I remains so after division. By the time we have developed into dozens or maybe hundreds of cells, every one of us picked the same asymmetry when there are two possible options. Let's arbitarily call them L and R. Every time, the developing foetus chose L.

How did it cross that threshold? It's not enough to say "it's in the genes"; There is no overt handedness to the zygote or even the blastocyst. There must be a root physical cause that always forces this "L symmetry" and never the "R symmetry".

The only thing I can think of is that the original proteins and enzymes and amino acids in that first cell have chirality. Some or all of them will not have mirror forms. And we pick up those proteins, enzymes and amino acids from our parents.

Presumably, tissues will form that have a "bias" of sorts - slightly more rigid in one direction, slightly more bendy in the other. So, as the tissues grow, they will form tissues that presumably will only "sploot" to the correct side, in the preferred direction. Since we all use the same proteins, we all have that handedness baked in.

Yes?

 

[DaveC426913]

To stave off an anticipated response, this is not an issue of evolutionary selection. We're not saying "any R symmetry strains would have been out-competed by the L strains."

That misses the point because it assumes this anatomical handedness is coded into the DNA. But that assumes anatomical handedness can be encoded in the DNA.

And that doesn't answer the question: how exactly could it be encoded? Unless it is via proteins and enzymes that physically constrain the tissues to always "sploot" preferentially as they grow..

 

[BillTre]

There are different kinds of asymmetry found in animals.

The kind you are talking about are kind of subtle deviations from perfect bilateral symmetry, like in the human body.
A lot has become known about this since I was a grad. student (1980s).

This stuff involves things like embryonic axes and how they get set-up in the cells of developing embryos. In general, a lot of this is known from many deep studies on a few organisms like mice, rats, fruit flies, zebrafish, and some lesser know organisms. They are easy to keep in the lab and have embryos that are easy to study, and have had a lot of research done on them.

Even the eggs of some invertebrates have different distributions of special molecules in different places in the cell. When the cell divides, one daughter cell gets a different load of molecules that the other (symmetry breaker). This can trigger a chain of events to produce asymmetries.
Any differences in the eggs would have been laid down when the mother constructed the egg in her ovary.

Normally (in vertebrates and their relatives) there is an embryonic process that sets the normal right and left sides. There is a mutation (situs inversus) that randomizes the process, so there is a 50-50 distribution of the normal and abnormal symmetries.
The mechanism involves the action of cilia on cells of the embryonic node (a thing in gastrulation when the first three basic tissue types are being determined). This makes a little flow in an important part of the developing embryo, which makes some diffusable factors go more to one side than the other. This leads to signally cascades in cells affecting their growth and/or determination (of their embryonic fate).
There may be a chirality in the cilia's microtubules (which is a spiral of tubulin proteins). The microtubules are a major structural component of the cilia and involved in their rotation which drives water flows by spinning one way or the other.
When this system operates properly each side is determined in a reproducible manner. The mutation shows this works, but all the little steps to each different kind of expression of the asymmetry are probably not known. For example, axons of the Mauthner cell (one on each side in the hindbrain) cross in a statistically predictable way (axons from one side usually cross over the top of those from the other side). This may just be from one side being slightly ahead of the other side in growing axons, but as far as I know no one knows.
Anyway the embryonic difference in signally is a symmetry breaker. From there developmental processes carry out further development slightly differently.

There are other examples in the animal world.
Starfish (I guess they're seastars now) and other apparently radially symmetric echinoderms (starfish, urchins, sea cucumbers) start out as bilateral embryos (after gastrulation) and then they transform into the apparently radially symmetric adults we are familiar with. They are not completely radially symmetric due to their single madreporite, off to the side on the top. It lets water into the tubefeet suction control system. They start out bilateral, curve together in a loop somehow and the sprout legs.

There are special cases of asymmetry like fiddler crabs. They have a big claw and a little by doing things like removing one claw or the other, it is possible to reverse the claw size symmetry, but they like to grow back the same. The bigger claw is connected to a bigger nerve ganglion in the body next to the claw. This is also thought to have some influence on the size of the claw that grows back. Innervation affecting regeneration is a common biological thing. The nerves can supply diffusable factors or small electrical currents.

To stave off an anticipated response, this is not an issue of evolutionary selection. We're not saying "any R symmetry strains would have been out-competed by the L strains."

There is an argument for this.
Snails with coiled shells have an asymmetry in that they usually coil in one direction. (there are mutations for that).
Hermit crabs live to occupy old empty snail shells. The shells have a handedness, so the crabs occupying them have a matching handedness. Their bodies that are inside the shell are asymmetrically twisted and weird looking, and their claws are also asymmetric. This is likely be adaptive, and therefore selected for, on the basis of fitting in the shell well provides better protect to the crab.