The physical properties of our bodies are mostly determined during the embryonic stage. The development of this main structure continues until we are 16-18 years of age without losing its symmetry. It is amazing, for instance that our ears have a similar shape and size, thus symmetrical, just as our arms are the same length, with perhaps only a slight difference (0.2%). The buds of the upper extremities (arms and hands) start developing during the 26th or 27th day of embryonic life, while the lower extremities (legs and feet) start during the 28th or 29th day. The developmental processes of the buds of the upper extremities and lower extremities are independent from one another. No signalization which causes the extremity buds to develop in a synchronized manner has yet been discovered during research. Symmetric growth is observable in many organs, including the fingers on our left and right hands. Even though we understand how our arms and legs develop, the question of how the coordination and control of the development of symmetric organs is maintained has still to be answered.

The miracle of life appears in the form of a baby which develops from a fertilized ovule (zygote) following millions of other events. This series of events, which is almost always the same for every fetus, can be grouped as reproduction, differentiation, and development. The zygote completes its development in the womb; postnatal growth can continue until 20 years of age. Even though every event during the baby's development seems to take place with chaotic reactions, harmony and order are there for us to discover. One of these astonishing events is the perfectly symmetric growth of the fetus/baby. Most organs in the human body appear in pairs and are symmetric. Babies are born with 300 bones; however, some bones later fuse with other bones, leaving only 208 bones in the adult human. It is still a mystery how long bones such as the humerus, radius, ulna, femur, and tibia are able to grow on both sides of the human body in a symmetrical manner.

Mechanisms that control growth in organs

In vertebrates, both internal developmental programs and the external factors which stimulate or inhibit growth play a role in the ultimate size of an organ. But the relative effects of these two mechanisms can vary significantly in different organs. When pieces of spleen from an embryo that is at a later stage of growth are transplanted to a newly developing embryo, each new piece grows, but not to the size of the original spleen. The total weight of all the transplanted spleen pieces is equal to a normal spleen's weight. When the spleen reaches a certain weight, growth inhibiting factors are secreted, which stimulate negative feedback mechanisms that limit growth. When a spleen reaches a certain size, the density of the inhibiting factors increases simultaneously, halting growth. Growth in the liver is controlled by extracellular factors (various substances in the blood, hormones, vitamins, minerals, etc.). When a section is cut off of the liver, the section continues growing and developing until it reaches the size of the original liver. The thymus has a growth process that is executed by a cellular genetic program. When sections of a thymus taken from the embryonic period are injected into developing mouse embryos, every section grows until it reaches the ultimate size.

More evidence of cellular growth programs was acquired via an experiment that was carried out with the salamander genus Ambystoma. When the leg bud of the larger species was injected into the smaller species, it would at first grow slowly, but then it would reach the normal size of its own species (the larger species).

Distinguishing growth and symmetry from one another

Both the arms and legs have long bones. A long bone consists of two parts (diaphysis and epiphysis). The diaphysis is the middle (core) part of the long bone. It consists of hard bone tissue, and is like a tube. The hyaline cartilage-covered joint forms the epiphysis of the long bone. In a growing bone, there is a growth plate (epiphysis plaque) made of hyaline cartilage; this is located between the diaphysis and the epiphysis. The epiphysis plaque causes the bone to grow longer; when growth is complete, the epiphysis plaque ossifies (becomes bone). In other words, growth stops. There are some clues that show the existence of positive feedback mechanisms which control the symmetric and balanced development of the arms and legs while the fetus is still growing. The arms and legs grow due to the development and growth of the plaques located at opposite ends of the long bone. The ultimate size of the arms and legs are proportional to the size of the finger bones (phalanx) and the metacarpus. According to current knowledge, growth in our arms and legs is only controlled by internal growth programs and the active growth of the plaques. We do not yet know the mechanism through which how much the bone must grow and symmetrically with the organ (the other arm or leg) on the other side of the body. But even if this is discovered in the future, we will continue to appreciate the perfect and miraculous aspect of this phenomenon.

In addition, in growth-plaque transplant experiments, the development of the transplanted growth plaque is dependent only on the age and size of the donor. Growth plaques cause the bone to grow, but the plaques themselves remain the same size for years. The cartilage cells they produce (chondrocytes) exchange places with the bone cells (osteocytes) in harmony and without destroying the length of the bone. Cells from different areas of the growth plaque act differently. Stem cells are found on the upper section, near the epiphysis. Immediately above them is an area where cells reproduce very quickly. At the bottom of the epiphysis, the cartilage cells grow up to 4 to 10 times larger than their normal size (hypertrophy). Cell reproduction here is mostly due to hypertrophic chondrocytes. The chondrocytes die and break up, then change places with the bone tissue. The dynamic process of these events in the growth plaque repels it from the bone area, and as a result, the bone grows longer.

Sustained symmetry despite cell sequence and speed of reproduction

The rapid growth rate in the legs and arms during the embryonic period continues to increase until the child is three years of age. This growth rate slows down until the individual reaches adolescence. During the fastest growth period, which is from adolescence to the early 20s, the growth rate rapidly increases. For example, most people who grow between 30 and 37.5 cm during the first two years of life can grow between another 7.5 and 10 cm every year during adolescence. At the onset of adolescence, rapid growth due to a sudden change in the volume of cells is observed. After adolescence a sudden falling off in the speed of growth can be observed due to the effect of hormones on the growth plaques in the spine and other long bones. The growth plaque now fuses with the neighboring cells and growth stops. However, the fusing of the growth plaque is the result of the cessation of growth, not the cause. After growth stops, the growth plaques begin to disappear. When the reproduction potential of the cartilage cells in the growth plaque has been exhausted, the growth plaque begins to disappear.

Growth plaques in different bones can trigger growth at various rates; these rates can differ as much as seven times. In fact, growth plaques on different ends of a bone can have different growth rates, provided that this rate is consistent with the genetic program. The number of cells on the growth line is 40 times more than in other areas. The number of cells produced here can exceed 10,000 cells per day. For symmetric growth between the arms and legs to be sustained, the number of cells in the growth plaque must be the same or very close. Experiments carried out on rats show that eight cartilage cells leave the growth plaque to exchange places with cells above them every day. It can be said that the growth of the bone is caused by the increase of cells in the growth plaque (which sustains its size). The growth rate caused by the growth plaque can be calculated by multiplying the growth plaque's cell production rate by the average length of all of its cells. Different growth plaques provide different growth rates. This difference can be caused by the difference in the size of the growth plaques, the difference in cell production rates, and/or the difference in the hypertrophy (growth) rate of every cell. The upper growth plaque in the tibia of mice generates 16,400 cells every day; the average life span of these cells is around 30 hours. Can such harmonious, symmetric, and equivalent growth in the arms and legs-despite the large number and variety of cells-be the work of pure coincidence, mindless nature, or unconscious molecules?

Do hormones play a role?

The main molecular players that organize longitudinal growth in bones during childhood are the growth hormone, the thyroid hormone, and corticoids. The sex hormones (androgens and estrogens) are programmed to influence growth during adolescence. Estrogen is the main determiner of characteristics related to increased height and an increase in bone quality, as well as adolescent-related physiology. These hormones are in charge of coordinating growth throughout the body. It is for this reason for women, after the menopause, the production in estrogen decreases and osteoporosis and brittle bones can occur. According to the current view, cartilage cells have a certain genetic reproduction potential, and when this potential finishes, growth stops. The growth rate during the embryonic period is 20 times higher than that of mid-childhood. The growth rate drops greatly during mid-childhood. If we exclude the noticeable increase during adolescence, the cells responsible for growth have begun to age. The bones on opposite sides of the body stay about the same size, despite all of these changes in growth rates. Circulating hormones and neuroendocrinal factors are believed to play important roles in maintaining symmetric growth. But there is no conclusive evidence to support this belief. Even though one can think of factors such as pressure, tension, and sports as helping control harmonious and symmetric growth of bones, no proof has been attained from controlled experiments. As a person ages, a gradual decrease in growth can be observed. Even if a growth plaque is placed into another organism, be it young or old, the growth rate of the bone does not change. This shows that symmetric growth in long bones is controlled by a program that is operated by internal factors, which is also compatible with the genetic program. When chemical-based medication is given to postpone growth, after the medication has been eliminated, the growth plaques grow faster for a short period to compensate for the lost time. These findings show that timing and the location and circumstances of the cell are critical parameters for reproduction. If the cartilage stem cells in the growth plaque have a certain reproduction potential, then it is clear that cartilage cell reproduction stops when growth comes to an end. If growth inhibiting factors slowly accumulate in the growth plaque, this might cause a deceleration of growth over time. Another possibility is some sort of "meter" in the unconscious and mindless stem cells, which keeps track of the number of cell divisions and thus controls aging. The estrogen in our body has a duty of closing down the growth plaques and speeding up the aging of cells. However, we should not forget that estrogen plays the special role of closing down all of the growth plaques at the same time. Estrogen is one of the visible causes of fertility, growth and development, and resilience. Estrogen also represents femininity and fertility at all levels.

When the signals from unconscious cells in the growth plaques and the quite sophisticated interactions among all the factors that influence growth, all of which require an all-encompassing knowledge to be executed, are taken into account, the impeccable genetic programs of different growth plaques on the two sides of the body that leads to the formation of the arms and legs, as if they have been molded in a factory, is absolutely amazing for anyone who reflects upon it.

References

• Wolpert L. (2010)."Unsolved Mystery: Arms and the Man: The Problem of Symmetric Growth." PLoS Biology. 2010 Vol. 8(9). pp 1-3
• Extremity Development during the Embryonic Period (www.visembryo.com)