Once the neuroblasts have reached their destination in the brain, they can further develop into neurons. The period during which the cells acquire their final shape and characteristics is called differentiation. This is a process that all neural cells go through, but not all at once. Neurons are differentiated first, followed by astrocytes, and finally by oligodendrocytes.

Important features of a neuron are of course the axon and the dendrites. During differentiation these features are formed. Initially, no difference can be detected between axons and dendrites. At this time, the cell body has a lot of small bulges called neurites. Eventually, 1 of these neurites will develop into the axon. This is caused by the fact that the tip of the neurite keeps growing. This tip is therefore also called the growth cone.

The surface of the growth cone consists of a kind of membrane, the lamellipodia. From this membrane come thin protrusions in all directions, these are called filopodia. The filopodia explore the environment and then retreat back into the lamellipodia. When a filopodia has found a very nice spot, however, it stays in this spot and does not retreat. At that point, the growth cone shifts to the tip of these filopodia, and the axon has grown a tiny bit.

However, a neuron needs more than a grown axon to function properly. The axon must grow in the right direction, so that it can later bind to cells that can do something with the signals the axon gives. There are several theories about this process, three of which will be described below.

Chemoaffinity hypothesis

This theory assumes that dendrites of cells release a certain substance. The substance released by the dendrites differs in different parts of the brain. The growing axons all have a preference for one of these substances, and therefore look for the route where this substance is most abundant. In this way the axons are guided to the part of the brain where this substance is released by the dendrites.

Blueprint hypothesis

According to this theory, growing axons are followed by a substance. A pioneer growth cone is the very first neurite that follows a certain route. This route is largely determined by chance. Successful axons leave behind more of the previously mentioned, unspecified, substance than unsuccessful axons. The new neurites now follow the route of the successful axon.

Topographic Gradient hypothesis.

Even before migration occurs, it is clear which cells will end up where in the brain. When migrating, the relative positions between different cells remain the same. The same is true for the relative positions between different parts of the brain. Axons use these relative positions to determine their path to their target.

There is also a process that ensures that axons all grow in the same direction. This is useful when the neurons from one area all connect to a specific other brain area. The process that makes this possible is called fasciculation. Here the axons are bound together, and grow as "one big axon" to their destination.

A remarkable fact about differentiation is that the process also occurs when a neuroblast is taken from the brain and put into another tissue. From this you can see that even before migration it is determined whether a neuroblast will become a neuron or another cell. So apparently something happened during the creation of the cells that gives the cell its ultimate purpose.

When axons and dendrites are formed, processes follow that allow neurons to send signals to each other. These processes are called myelination and synaptogenesis.

Author: Myrthe Princen (translated by Thomas von Rein)