The reason why the heart grows on the left is because of this missing organ.

Why does the heart grow to the left? it starts before it starts to develop. Some genes are no longer present after a few hours of expression during this period. And it is these "retirement" genes that make you and me healthy.

In a dream, you are fighting with a bad guy with a blurred face. You are gradually in a weak position and are forced to the edge of a cliff, when he throws a hard punch at you, and you feel like you are starting to fall, and then you are scared to wake up. You realize that you are in a familiar environment, but you are still in a bit of a panic, so you subconsciously move your hand to the left side of your chest. The continuous, steady and powerful beating there gradually makes you feel at ease.

If 10,000 people wake up from this nightmare at the same time, one person may not touch the left side of his chest, but touch the middle or more right position. They have a special situation-heterotaxy, which means that their heart or other internal organs are not in the same position as most people.

According to some scientific observations, if a person has total visceral inversion (situs inversus totalis, the visceral position is mirrored symmetrically with normal people), it may be harmless. According to a review article posted on Developmental Cell, the oldest woman in Europe lived to be 126 years old, and she had total visceral inversion. The biggest problem may be that when she is ill, it will be more troublesome to see a doctor or operate on her.

If it were not for total visceral inversion, the situation would be even worse. This means that the person may have a left-right body axis axis defects, and he is likely to suffer from some congenital diseases. Moreover, we have little chance of seeing him because he may have died during the fetus.

A symmetrical body, an asymmetric heart.

99% of animals, including humans, are mirror symmetrical in their external form, which is also known as bilateral symmetry in biology. The human body has two basic axes, namely the front-rear axis and the upper-lower axis. The front-rear axis determines the direction of the human body, and the organs that perceive the environment and come into contact with food will be located in front of the person. When the human body moves forward, the symmetrical body can help us reduce resistance and save energy. In the ancient times when resources were scarce, the key to the continuation of life lies in the efficient acquisition and preservation of energy.

Thus it can be seen that the external form of people and animals is largely shaped by the environment. However, the influence of the environment on the internal organs is not so strong, at least the internal organs do not need to be symmetrical, only the weight distributed on the left and right sides is about the same. It is also true that the human heart is located on the left side of the central axis of the human body and on the right side, and the stomach and liver are mainly distributed symmetrically.

As mentioned at the beginning, this pattern of organ distribution is "copy-paste" in 99.99% of people. This is an accurate process of biological development, but why does it have to be? scientists from Singapore recently published a study in Nature Medicine, revealing the genes that play a key role in the early development of the human body. unravel the mystery of why the fresh heart beats on the left side of the body.

The "organizer" in the embryo

In the late 20th century, Japanese scientists found that when a mouse embryo is in the blastocyst stage, its lateral mesoderm (lateral plate mesoderm, the inside of which attaches to the endoderm to form the visceral layer) has movable cilia on some of the cells that guide the embryo's development, allowing the embryo fluid to flow clockwise, that is, from right to left. They believe that this process may be common in animals-this flow activates genes that are only expressed on the left side of the cell, causing the left and right sides of the embryo to develop asymmetrically-so that internal organs can form and develop in the right place.

However, this view was quickly refuted, and some subsequent studies have found that in embryos of animals such as birds and pigs, cells that guide embryonic development form a temporary organ, the left and right tissue organ (left-right organizer,LRO), but there is no movable "cilia" on it.

In fact, LRO is present in all animals and is critical to determining the arrangement of organs from the left to the right of the body. In many animals, LRO refers to a layer of cells with cilia on the surface. In mouse embryos, the cilia on the cells in the middle region of the LRO can be up to 8 microns long, mainly causing the embryo fluid to flow from the right to the left, while there are 4 microns of cilia around them, which do not move, but act as baroreceptors. What the LRO of bird and pig embryos do not have is those 8 micron cilia.

Fortunately, like mice, this organ has movable "cilia". In other words, the findings of Japanese scientists may make sense in the human body. In the new study, the researchers cleverly took advantage of the findings: there are no "cilia" on the LRO of birds and pigs, but there are in humans, mice, fish and amphibians, which means that during the period of the emergence of "cilia", some genes are only expressed in these animals, which may play a key role in determining the location of organ development. Not surprisingly, the researchers found five genes.

Mutations in organs

In fact, all five genes are involved in the proteins of the cells that encode LRO. Among them, three genes (PKD1L1, MMP21 and DAND5) have been confirmed to be associated with visceral ectopic. Another gene, CIROP, which is newly discovered in this experiment, can express a metal enzyme. The researchers speculate that the reason it has not been discovered before may be that it was only expressed in early blastocysts for a few hours and then did not work.

They first conducted an experiment with zebrafish: the CIROP gene of the female zebrafish was knocked out before it could ovulate normally. This will not affect fertility, but also can obtain zebrafish embryos without CIROP gene. They observed organ ectopia in developing zebrafish embryos.

When the organs in animals begin to develop asymmetrically, the heart is one of the earliest organs to develop. They found that after 48 hours of development, zebrafish fertilized eggs lost the CIROP gene, and the blood circulation tubes in the heart (cardiac looping, which initially turned into a spiral loop, usually counterclockwise) became messy and random. And not only the heart, but also other organs will be affected.

They also found that in Xenopus embryos, inhibiting the expression of the CIROP gene on the left side of LRO affected the asymmetric development of organs, while removing the CIROP gene on the right had no effect. Subsequently, the researchers further confirmed that the flow of embryonic fluid controlled by LRO regulates the expression of the CIROP gene on its left, which controls the asymmetric development of organs.

Ectopic organ

Considering that humans, fish and amphibians share the same LRO, the researchers speculate that if there is a mutation in human CIROP, it may have the same problem as zebrafish and Xenopus laevis, that is, organ ectopia. They sequenced the genes of 186 people with coronary heart disease and found 12 families with CIROP mutations living in different regions. In these 12 families, a total of 21 people have CIROP gene mutations in the genome, a total of 9 forms of mutation.

Of the 21 people with CIROP mutations, eight had no ectopic organs other than the heart, some had a right heart (isolated dextrocardia, with the heart on the right) but developed normally, five had blurred visceral distribution (situs ambiguus), and eight had total visceral inversion (situs inversus totalis), similar to the previous woman who lived to be 126 years old. A