There has to be a map for size and shape of organs stored in genome.Is this riddle solved?

Genes are turned-on and off at different stages of development. They're controlled by "chemical switches" that attach to genes responsible for the physical characteristics we see. Timing in biology via these chemical switches (e.g. methylation) is highly regulated - believe it or not, this idea goes back to Aristotle and is often referred to as epigenesis.

A convenient way to consider how controlled development is achieved is to treat it as a process that consists of synthesizing a particular substance at a particular time and at a particular place. The timing of some aspects of development involves a rigid sequence: Event B cannot occur before A, nor can C occur before B, and so on. Development unfolds because of a sequence of events, each one the direct cause of the next.

Once an organ reaches a desirable adult size, the genes responsible for its growth are turned off permanently. This is why humans cannot regrow amputated limbs, for example.

Thanks for your reply. But sadly this is not sufficient. Let us assume an organ of a shape of a sphere with 10mm diameter. Cells must stop growing when the diameter of a ball reaches 10mm. Since there is no mechanism of measuring, outer most cell must know its location on 3D map. Which means every cell must have a sensor to detect its position. And sphere is a geometric object. Most organs are not geometric and so the task of signalling becomes extremely difficult.

Before ON/OFF signals are sent to the growing cells, there has to be two measurements. One of space and the other of time. So what is the yardstick and clock? And presumably these have to be located in every cell because growth of all of our organs is not uniform.

If a part of our liver is cut off, that portion is grown again but how it maintains its size in 3D? It seems to me that we do not have clear understanding of the mechanism involved.

A very valid point.

I think the best way to approach this answer is by understanding why cancer cells don't follow the same instructions. In other words, what causes cancer cells that arise from liver tissue to grow continuously forming a tumor, while healthy liver cells "know" when to die and regenerate new cells. In fact, liver mass is proportional to one's body size - bigger people have bigger livers than smaller people.

To study liver size, a study was conducted on mice where it was found that bile acids regulate liver regeneration, and might also help determine liver size. Bile acid synthesis is regulated by cytochrome P450, polypeptide 1 (CYP7A1) - this endoplasmic reticulum membrane protein catalyzes the first reaction in the cholesterol catabolic pathway in the liver, which converts cholesterol to bile acids. The expression of CYP7A1 is down-regulated by of FGF19 (in mice, FGF15), produced in the intestine.

When livers of FRGN mice can be destroyed and then fully repopulated with human hepatocytes, the humanized livers grow to a larger size than the original mouse liver. The humanized livers also express higher levels of CYP7A1. This is because the human liver cells do not recognize the mouse FGF15 - they only respond to the human form, FGF19.  The high expression of CYP7A1 in the humanized livers leads to high production of bile acids.

The researchers then investigated whether FGF19 regulation of CYP7A1 and bile acid production control liver size in FRGN mice

They inserted the gene encoding human FGF19, including its regulatory sequences, into the FRGN mice to create FRGN19+ mice. Livers of FRGN19+ mice and their FRGN littermates were then fully repopulated with human hepatocytes.

As previously observed, livers were larger in FRGN mice with humanized livers (13% of body weight), compared with control FRGN mice, due to increased hepatocyte proliferation; FRGN mice with humanized livers also had much larger bile acid pools and aberrant bile acid signaling. However, livers from FRGN19+ were normalized, to 7.8% of body weight; their bile acid pool and signaling more closely resembled that of control mice.

The authors concluded that FGF19 intestine–liver signaling controls bile acid homeostasis and liver size.

Please read the rest here: https://journalsblog.gastro.org/what-controls-liver-size/

I believe the take home message here is that the science is incomplete, but we're getting to the point of understanding how liver size is regulated in animals. In addition, regulation of organ size also depends on the organ. Obviously, the pathway that regulates liver is different than what regulates kidneys, so each one would need to be investigated individually. There's no simple black or white answer for your question, apart from what I generally wrote in my initial post.

Thanks for pointing out a very fascinating experiment, I am good at logic and intend to apply it to biology. But the task appears to be enormous because present knowledge of biology is enormous; even if I neglect chemistry.
In your earlier post you mentioned Aristotle. Even at his time logical reasoning led to surprisingly correct conclusions. One philosopher concluded that sun is far bigger than the earth and so it is likely that earth revolves around the sun.
Somebody pointed out, ‘if so, how do you explain periodic day and night?’
Philosopher said (don’t remember his name) ‘It can be explained if we assume that earth also revolves around itself’
All these modern concepts were arrived at simply by applying logic. But logical deduction can be wrong as well. Aristotle rejected this idea because when a coin is dropped it falls just under it and not further away, which should happen if the earth surface is rotating.
Many centuries later, but before Galileo and Newton, one scientist answered Aristotle’s objection by reasoning that coin must also be rotating along with the earth.
Only yesterday I came across a new branch, ‘Philosophy of Biology’. I  wonder if the speculations are made by the authors, based on logic applied to known observations. I don’t know if I will be able to go through it as I dislike philosophy.
At this point I will be happy if you answer my following question.
Organ grows with a beginning of one or few cells, which grow in all directions till the intended size is reached. Do all cells undergo mitosis or only the cells at the surface? Too much of a force will be required to push away large mass of the surrounding cells, if internal cells also duplicate.

I really like this question because I was once asked something very similar by a friend who studied accounting - I was only a student then. He asked, when a carrot grows underground, why isn't the inside of the carrot dirty too? The same idea can be applied to beets, yams, potatoes, or anything that grows underground. Hence it really got me thinking then, and it also applies to what you're asking here. Does the skin of the potato fully form first, and subsequently get filled and expanded as the flesh of the vegetable grows in?

Answer this, and you'll get the answer to your question.

I am not sure but I think skin, being a protection for a potato, must be formed first and will grow with the intake of flesh. If true, this would mean that cells of the outer boundary contain the information of shape of an organ. Please correct me if I am wrong. 

I believe your assumption is correct, all "seed potatoes" start off looking like a shriveled old potato that sprout and fill-up overtime.

Thus, I think the two concepts relate well to one another. Information for size is programmed in a group of cells very early on in development. As cells in tissue grow, when those outer cells reach a critical mass, they send signals to the inner cells to stop growing. Usually these signals are sent via receptors (presumably stretch receptors) found on the outside of the cell membrane.

In one famous 1960s experiment, researchers implanted 6 or 12 fetal mouse spleens into individual adult mice whose own spleens had been removed. They found that each implanted spleen grew to a proportional fraction of the size of a normal adult mouse spleen, leaving the animal with a normal total amount of spleen material. This suggests that spleen tissue has a way of understanding how much of it there is in relation to the body. When the same experiment was conducted with the thymus, the same researcher found that multiple thymus grafts implanted in an adult mouse behave completely differently: each grows to its full adult size.

Thanks for bringing to my notice this non uniformity in development of organs. I came across such experiments before. I also know that a group of cells of one organ, implanted in the other, either change their fate and redevelop into similar to those surrounding them or undergo apostasis. But I thought that behavior of cells under changed environment is uniform.
To avoid cancerous growth, cells of thymus must communicate. Surprising  part is that they are able to distinguish between their own community and that of their neighborhood, even though nature of signals is expected to be same. 

So I'm assuming you knowing about this earlier study:



In a 1930s experiment, scientists took limb buds from a small salamander species and transplanted them onto a larger salamander species, and vice versa. They found that the size of regenerated limbs was controlled by the transplanted tissue, not the recipient. Somehow, salamander limb buds seem to "known" what size they should grow to. 👍

No. I have started reading biology on ly recently.
This is a thought provoking experiment. It not only suggests that map of size  and shape is local to the cells of the organ and that growth factor has a very limited role to play. It could be just a master clock for all organs.
It would be interesting to study various pathways and the difference between them and why that difference exists.
Whatever I wanted to introduce in Biology, is already introduced. Verbose logic is covered by Philosophy, Digital gates are used to represent pathways and when I searched for programming in biology, this too is already present. And still, nature did not use logic for development. It used evolution. This is why. I think, logical  methods will find limited use and will have to be used cautiously. But this possibility of applying all sciences and skills in biology will make it a queen of all sciences.

Right. The information for size seems to be pre-programmed in that group of cells very early on, and they don't care what was happening in the animal.


 The only time I reached the same realization about biology was when I took a development biology course in year-3 university. I walked into class thinking it'd all be about meiosis and fetal development, but man was I wrong. We investigated how a variety of interacting processes generate an organism's shapes, size, and structural features, meanwhile discussing how the product of various genes interact with one another in a timely, organized, and sequential manner. If you want to be convinced that biology is in fact the queen of all sciences, I suggest you look into taking a development biology course online. The one linked isn't the best, but it's free nonetheless.

Thanks for your suggestion. I will keep this in mind.
My experience is same as that of yours. I started with the cell and was amazed the way transcription and translation took place and bewildered by in built in process of correcting defects.
Then I came across , 'Develolpmental Biology' a book by Gilbert.
It gave me Goosebumps. I felt like an Old Man in the Wonderland, with a difference that this wonderland is for real.
By the way, this forum needs to include topic on Logical Biology.