Animals can stand when they are born, so why can’t human babies?

Ren Shengquan

Many people have long wondered why mammals such as cows and horses can stand up at birth, while humans need a long time to walk. Zoologists have calculated that babies need to stay in their mothers' wombs for 18-21 months before they can walk like other animals do at birth. Due to the limitations of the pelvis, the average gestation period of a human fetus is only 9 months, which means that babies cannot walk until they are one year old. If we use scientific principles to explain this, it involves the ability of nerves to control muscles.

Recently, researchers from the University of California, San Diego, inadvertently "unlocked" the ability of nerves to control muscles through structural biology. Their research results were published in the international journal Nature, which will provide new ideas for the treatment of myasthenia gravis.
Muscle force is achieved through muscle fiber contraction, which requires motor neurons to control skeletal muscles. The key lies in the neuromuscular junction, which is the connection point between motor neurons and skeletal muscle fibers.

Scientists have studied the working mode of the neuromuscular junction for more than a century and finally determined that acetylcholine released from the motor neuron terminals acts like a key to open the acetylcholine receptors on skeletal muscle cells, thereby initiating strong contraction of muscle fibers.

In the latest study, scientists used cryo-electron microscopy to obtain high-resolution three-dimensional structures of muscle acetylcholine receptors when bound or not bound to acetylcholine. The challenge of this work first comes from the acquisition of samples. The weight of acetylcholine receptors in skeletal muscle is extremely low, and it is difficult to obtain enough tissue samples if they are to be isolated from human muscle.
Therefore, the researchers thought of obtaining beef, which is easy to obtain and contains more acetylcholine, and turned to obtaining muscles from cow embryos. In the end, they obtained 30 micrograms of purified acetylcholine receptors from each kilogram of beef.

After studying the high-definition three-dimensional structure of muscle acetylcholine receptors, researchers unexpectedly discovered that two versions of the receptor can be seen simultaneously in the same embryonic tissue sample: an immature embryonic version and a mature neuromuscular junction version. The subunit composition of the two versions is different.

Normally, as the neuromuscular junction matures, the acetylcholine receptor needs to complete subunit conversion, but the structural principle of how it changes from the embryonic type to the mature type is not clear. Now researchers clearly see two versions of acetylcholine receptors in the early muscle tissue of cattle embryos, one that promotes the formation of connections between nerve endings and muscles, and the other that controls muscle contraction.

At the same time, the question of why mammals like cows and horses can walk on the day they are born has been answered: from the perspective of muscles, it turns out that cows and horses have completed the developmental transformation of acetylcholine receptor subunit composition before birth and formed mature neuromuscular junctions, while humans are not born with the ability to control skeletal muscle contraction. In the first few months after birth, humans have poor muscle coordination and usually need about a year to form mature neuromuscular junctions.

This study officially unlocked the working mode of the neuromuscular junction, bringing good news to patients with myasthenia gravis, because its root cause is the damage to the neuromuscular junction, which makes patients unable to effectively control the contraction and force of skeletal muscles.

(The author is a health manager and a member of the Anhui Science Writers Association)