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How Mammals Maintain Symmetry During Development (scientificamerican.com)
79 points by extarial 5 months ago | hide | past | web | favorite | 16 comments

> They found that the cells surrounding the suppressed tissue communicated with the placenta, which then signaled the rest of the organism’s tissues—including the other hind leg—to slow their growth until the hindered limb caught up.

Can somebody dumb it down for me? It's fascinating but I still don't understand how do they communicate. Is it done through nervous system? Presumably not because it's not reaching all tissues and it's probably not yet fully developed at that point. So how does it happen? If it's just releasing some chemicals it seems hard to imagine that it could be accurate. Plus how would the slower limb know that these chemicals come from it and it does not need to slow down growth. How does something know that it is slower than it should be? So many questions.

At this point of development, the communication is done via release of chemical factors which bind to other cells and cause changes. The general problem of pattern formation in embryonic development has been extensively studied; see here: https://en.wikipedia.org/wiki/Pattern_formation and https://en.wikipedia.org/wiki/Reaction%E2%80%93diffusion_sys...

I'm oversimplifying, bjut it's basically the gradient of a chemical that acts as a control variable.

The associated paper to the article is:


p.15 has a summary of what they propose, e.g., density of p21+ chondrocytes, as an inhibitor:

"Because we found that the extent of compensatory proliferation does not linearly correlate with cell density—but it does with the proportion of p21+ chondrocytes — we posit that density plays a permissive rather than an instructive role and that stress signals emanating from p21+ chondrocytes are needed as well."

that's text I can't interpret, unfortunately. It's highly speculative and ambiguous.

Recently there's been some conjecture that bioelectricity guides embryonic development as well: https://www.quantamagazine.org/brainless-embryos-suggest-bio...

From a layman's perspective, there are some really exciting developments happening in the field of morphogenesis!

Yes it's "just releasing some chemicals", vast and complex regulatory networks of chemicals.

They then did RNAseq experiments (measures which genes are transcribed [are active]) in the two legs separately and looked for statistically significant differences (which genes are active in the injected leg but not the other one?) and found:

"enrichment of several pathways related to stress and immune responses in the left cartilage.In particular, we found several stress-related transcripts that shared a similar left–right pattern of expression within each embryo"

Theory of growth control, Shang

Also neural crest cells.

A good book is the spark in the machine . It’s more of speculative literature tying past scientific studies in medical history with predictions ancient Chinese physicians made with how energy flows through the body vis conductive fascial pathways. Heavily covers embryonic development and formation of our body

Your questions seems to me very important, thanks for phrasing them in a much better way than I did.

(I just posted at the same time as you)

My kid was always 90+ percentile for height when she was younger. Then when she got an expander (ortho stuff) she stopped growing almost completely for about a year. Then she seemed to resume growing. I have wondered if putting stresses in the jaw forcing it to expand may have triggered something that slowed her growth. Or perhaps it was a coincidence that she plateaued at that time. Now I see this:

>> They found that the cells surrounding the suppressed tissue communicated with the placenta, which then signaled the rest of the organism’s tissues—including the other hind leg—to slow their growth until the hindered limb caught up.

This makes me want someone to study kids growth before, during, and after things like orthodontic treatments. Maybe it really wasn't a coincidence. Putting pressure on the bones to force them apart may have signaled the rest of the body that one part needed to catch up and so the rest slowed down.

This concept seems fascinating.

Original article:

Roselló-Díez A., Madisen L., Bastide S., Zeng H., Joyner A.L. "Cell-nonautonomous local and systemic responses to cell arrest enable long-bone catch-up growth in developing mice." PLoS Biol. 2018 Jun 26;16(6):e2005086. doi:10.1371/journal.pbio.2005086


Can someone having knowledge in this dark art:

* tell what is the messaging system (I understand it is some kind of IGF peptides),

* what are the semantics of the messaging system (how can it report about the length of a limb? how are identified senders and receivers?)

* what is the controlling system (which compares the two limb lengths and corrects the lengths by sending other messages?)

Many thanks!

It's hard to answer these questions because you're asking like a human engineer how another rationally designed system "works" via agency and intent. Biology doesn't work that way.

But yes: the data is signalled in the form of pools of individual molecules. The messaging system uses tags to target molecules (in some cases) or just controlled spatial relase to target the messages.

The controlling system is a complex set of genetically regulated proteins and other components.

See morte here: https://en.wikipedia.org/wiki/Cellular_communication_(biolog...

None of this is fully understood but it has been extremely successful in explaining a lot of more complex developmental phenotypes.

Interesting, but remember this regards external symmetry. Most mammals have an internal asymmetry of organ placement.

In humans, there is a condition Situs inversus in which internal asymmetry is reversed (i.e. organ placement is mirrored):


Incredibly, the internal asymmetry of mice has been experimentally reversed:


See also Adolf Portmann's strange speculations on symmetry and asymmetry:


extract from that page: https://imgur.com/a/IAB12T5

"According to Portmann in animals all organs that cannot be arranged symmetrically are concealed under non-transparent covers. All types of animals that are glass-clear, completely transparent (ctenophorans, water-fleas, etc.) demonstrate "an important rule in primary animal reproduction: their whole organisation is uniformly symmetrical. Whether they are radial or bilateral this building plan regulates all organs to the deepest point".

Portmann refers to all the visible optical structures characterized by a symmetrical construction as "organs of view, whose entire appearance only makes sense if we consider it as directed to the eye, be it the eye of another animal of the same species of the eye of an enemy".

It goes on. Portmann is out of fashion, I believe, maybe seen as an eccentric or even discredited. I read about this idea in an interview with the artist Pierre Huyghe.

It always amazes me how life handles exceptions, this kind of studies remind me of QA testers trying to break my code. Scientists being the testers, the body being the application, and DNA being the code.

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