Development of the nervous system

The development of the nervous system is one of the most fascinating and complex processes in nature. It is the way animals, including humans, build their nervous systems from the very early stages of life right through to adulthood. This process, also called neural development or neurodevelopment, creates the brain and spinal cord and helps form the pathways that allow our bodies to send and receive signals.

In animals with a backbone, called vertebrates, this journey begins when a special tube forms from the outer layer of cells during early growth. This tube then becomes the brain and spinal cord. After that, new cells called neurons are born, move to their correct places, and connect with each other to form networks. These connections are shaped by activity, helping the nervous system work properly.

Scientists study neural development using tools like special types of genetic testing and live imaging. These tools help them see exactly what is happening inside cells as the nervous system forms. Problems during this development can sometimes lead to health issues, such as balance problems, trouble with movement, or seizures. Understanding neural development helps scientists learn more about how the brain and nervous system grow and stay healthy.

Development of the nervous system in humans
nervous system
embryonic development
neuroscience
developmental biology
nematodes
fruit flies
mammals
holoprosencephaly
neurological disorders
limb paresis
paralysis
seizures
humans
Rett syndrome
Down syndrome
intellectual disability

Vertebrate brain development

The central nervous system in animals starts from a special part of the embryo's outer layer. This part becomes a shape called the neural plate. The neural plate folds and forms a tube called the neural tube. This tube grows and splits into three main parts that become the forebrain, midbrain, and hindbrain.

As the embryo grows, these parts split further into smaller sections that develop into different parts of the brain and spinal cord. The neural tube is filled with fluid that helps shape the brain. Cells inside the tube divide and turn into neurons and other brain cells. These neurons move to different places in the brain and connect with each other to form pathways that help the brain work.

Induction

During early development of animals with a backbone, a special layer of cells called the ectoderm starts to change. Part of this layer becomes the skin, while another part becomes the nervous system. This change happens because of signals from another layer of cells called the mesoderm.

As the embryo grows, cells move and form a structure called the notochord, which later becomes part of the backbone. The cells above the notochord then form a flat piece called the neural plate. This plate folds up to make a tube, which will become the brain and spinal cord. This process of forming the nervous system from a simple layer of cells is called neural induction.

Regionalization

Later in development, the top part of the neural tube bends at the place where the future midbrain, called the mesencephalon, will be. Above the mesencephalon is the prosencephalon, which will become the forebrain, and below it is the rhombencephalon, which will become the hindbrain.

The front part of the prosencephalon grows to form the telencephalon, which develops into the cerebral hemispheres. The main part of the prosencephalon becomes the diencephalon. The optical vesicle forms here and later becomes parts of the eye, including the optic nerve, retina, and iris.

Patterning

In chordates, the top layer of skin cells forms all the parts of the nervous system. This happens because of special conditions — different amounts of signaling molecules around.

The bottom half of the early nervous system shape is guided by the notochord, which acts like a director. The top half is guided by the skin layer next to it.

The skin layer normally becomes nerve tissue. Tests with single skin cells show they can become nerve cells because they lack certain blocking signals. The director might make molecules that stop these blocks.

The bottom part of the nerve tube is shaped by a signal from the notochord. This signal tells cells to become different types of nerve cells depending on how strong the signal is.

The top part of the nerve tube is shaped by signals from the surrounding skin layer. These signals help create sense-related nerve cells.

Signals like FGF and retinoic acid help decide how the front and back parts of the nervous system develop. For example, in the lower part of the brain, special genes called Hox genes help decide where different nerves form.

Neurogenesis

Neurogenesis is the process where neurons are created from special cells called neural stem cells and progenitor cells. Once formed, neurons stop dividing and do not divide again for the rest of an organism's life.

Changes in how genes work help control these processes. These changes, called epigenetic modifications, are important for deciding what kind of cells these stem cells will become. These modifications include adding and removing certain chemicals from DNA, which helps guide the development of neurons in both growing and adult brains.

Neuronal migration

Neurons move from where they are first made to where they will work in the brain. They can travel in different ways, such as by radial migration or tangential migration. Scientists have watched these movements using special microscopes.

Neurons start in a special area and move out to form early layers of the brain. Some neurons move using radial glial cells, which act like guides. These cells help neurons move to their right places.

Most neurons that help with quick signals move sideways to reach the right spots in the brain. For example, some neurons travel from an area near the bottom of the brain to the top part.

Some neurons follow existing nerve paths to move. These neurons can travel long distances, like from the nose to the brain.

There is also a type of movement where neurons have many branches and move in different directions. These neurons are found in the middle layers of the developing brain.

Neurotrophic factors

Special helper parts, called trophic factors, help keep brain cells, called neurons, alive. Scientists Victor Hamburger and Rita Levi Montalcini discovered that when an extra limb was added to a growing chick, more brain cells stayed alive. They found that brain cells often stop working and disappear during normal growth, but the extra limb helped keep more cells alive.

One important helper part is Nerve Growth Factor (NGF), which was discovered by Rita Levi Montalcini and Stanley Cohen. There are also three related helper parts called BDNF, NT3, and NT4 that help different groups of brain cells stay alive. These helper parts work by connecting to special parts on the brain cells to send important messages inside the cell. Other helper parts, like CNTF and GDNF, also help keep certain brain cells alive by sending similar messages.

Synapse formation

Neuromuscular junction

Main article: Neuromuscular junction

Much of what we know about how connections form in the nervous system comes from studies at the neuromuscular junction. This is a special place where nerves meet muscles. A chemical called acetylcholine is used to send messages at this junction. Before a nerve connects to a muscle, the muscle already has receptors for acetylcholine. When a nerve arrives, it helps group these receptors together at the connection point. Research has shown that a substance called Agrin, made by the nerve, is important for grouping these receptors and forming the connection.

CNS synapses

In the brain and spinal cord, different signals help connections form. Neurons can grow and connect in simple cultures, showing that they have the ability to form connections on their own. Studies have focused on connections that use a chemical called glutamate. During development, the branches of neurons move around a lot and often start touching other neurons first. This touch can lead to the formation of new connections.

Assembly of neural circuits

The way neurons move, change, and find their paths is usually thought to be guided by built-in genetic instructions. However, activity — like electrical signals in the neurons — also plays a role in shaping these paths and connections. There are two main types of early activity in developing neural circuits: spontaneous activity, which happens on its own, and activity caused by sensory input, which comes later. Spontaneous activity is seen in many parts of the developing brain and helps create early maps and connections. For example, in the developing visual system, waves of activity help form maps that tell the brain where things are in space.

Research using different methods has helped us understand these early signals. In the auditory system, bursts of activity help organize connections based on sound frequencies. In the motor system, spontaneous activity helps coordinate movements and connect new cells into circuits. In the developing spinal cord of fish, early activity helps organize rhythms for swimming. As the brain matures, connections are refined further by actual sensory experiences.

Synapse elimination

Main article: Synaptic pruning

When the nervous system is growing, it first makes extra connections between nerve cells to reach all the cells it needs to control. Later, the system gets rid of some of these extra connections. This helps make the nervous system work better by keeping only the strongest and most used connections. This process is important for building effective pathways in the developing brain and body.

Mapping

Brain mapping can show how an animal's brain changes as it grows. In 2021, scientists studied the brains of eight tiny worms called C. elegans from the start of their lives to adulthood. They also looked at how the connections in a muscle of a mammal, like a mouse or a person, change from when a baby is born until they are fully grown.

Adult neurogenesis

Main article: Adult neurogenesis

New brain cells, called neurons, can form in adults just like they do when we are growing inside our mothers. This happens in special parts of the brain, such as a place called the dentate gyrus of the hippocampus. Scientists first discovered this in rats a long time ago, showing that our brains keep changing even after we are fully grown.