Neuronal migration: this is how nerve cells move

Our brain is made up of a large number of neurons that fit together like a huge puzzle. Thanks to the fact that all of them are in their correct position, our nervous system can function at full capacity and without any problem.

However, neurons are no longer born in their final position. Rather, they are formed in another region of the nervous system and must travel a long way to reach their destination. This phase of brain formation is known as neuronal migration.. Any abnormality in its development can cause serious malformations in our nervous system and as a consequence a large number of neurological disorders.

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What is neural migration?

Our brain is made up of hundreds of thousands of neurons. A large number of these nerve cells originate in locations other than those they will occupy once they reach adulthood.

This process is known as neuronal migration, and most of it occurs during embryonic development, specifically between 12 and 20 weeks of gestation. During this period, neurons are generated and travel through our brain until they settle in their final position.

This displacement is possible thanks to the signals coming from other neurons, which are already in their final position and exert a role similar to that of a traffic light directing traffic, sending different types of signals to which neurons in the process of migration.

This migratory process occurs from the ventricular zone of the neural tube, the place where the neurons originate, to the place designated for them. During the beginning of neuronal migration, these cells located between the ventricular zone and the marginal zone, which form the intermediate zone, a space of transitory location.

Neuronal migration occurs in different phases and is highly complicated. since these nerve cells must travel a great distance and avoid numerous obstacles so that the brain can develop fully and satisfactorily. For it, They are helped by a type of cells that form what is known as radial glia, and that exerts the function of scaffolding through which the migrating neurons move.

When some of these phases of neuronal migration are not carried out correctly, they can appear from changes in the organization of the brain, to brain malformations very important.

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Migration phases

As mentioned in the previous section, the neuronal migration process occurs in different phases, specifically in three, of which each and every one of them are essential for a cortical formation successful. These stages of neuronal migration are as follows.

1. Cell proliferation phase

In this first phase, which occurs from day 32 of the gestational cycle, nerve cells or neurons originate.

A large number of these neurons are born in the germinal zones or germinal matrices, hence the name of the phase. These zones are located in the walls of the lateral ventricles.

2. neural migration phase

Throughout this second phase in when the neuronal migration itself occurs. That is, the neurons leave their place of origin to head towards their final position.

This process occurs thanks to the glial radial system. In this system, a cell that is no longer present in the adult brain guides neurons to their position.

3. Horizontal and vertical organization phase

In this last phase, the differentiation and subsequent organization of neurons takes place. Due to the complexity of this final stage, what it consists of and what its particularities are will be explained below.

How does differentiation occur?

When the neuron has managed to reach its final location, the differentiation phase begins., achieving all the morphological and physiological qualities of a fully developed neuron. This differentiation depends both on how said neuron is genetically preconfigured, as well as on the interaction with other neurons and the creation of connection pathways.

In our nervous system, as well as in the rest of vertebrates, the neural cells differentiate from each other as a result of different progenitor cells; which are located in specific locations of the neural tube.

Once the differentiation process is finished, neurons organize themselves by linking to each other, ending the process of neural migration and completely ending the development of our brain.

Defects in this biological process

As detailed in the first point, any abnormality in the course of neuronal migration can have consequences on the formation of our brain; from malformations to alterations in brain organization.

The most serious malformations are associated with alterations in intellectual development and epilepsy, while in organizational problems the brain has a correct external appearance but neural connections are badly damaged because its correct disposition in the brain did not take place.

Among the causes of these failures are:

• Complete migration failure.
• Interrupted or incomplete migration.
• Diverted migration to another brain location.
• No stop migration.

Regarding the consequences of these defects in migration. An abnormal development of the process can give rise to a large number of disorders and disorders. Among these disorders we can find:

1. lissencephaly

The lissencephaly It is the most serious consequence of a failure in neuronal migration. In this case, the neurons start their migration but are not able to complete it, which causes serious deformities in the brain.

Depending on the severity of the malformation, lissencephaly can be divided into three different subtypes:

• Mild lissencephaly: this type of malformation causes Fukuyama congenital muscular dystrophy, which is characterized by occasional hypotonia, frailty and general exhaustion in the child, intellectual development disorder and epilepsy.
• Moderate lissencephaly: the direct consequence of this degree of lissencephaly is Brain Eye Muscle Disease, whose symptoms are intellectual development disorder, myoclonic seizures and congenital muscular dystrophy.
• severe lissencephaly: is externalized by the Walder-Walburg Syndrome, which causes serious abnormalities in the nervous system, eye pathologies and muscular dystrophy. Patients born with this type of malformation die at a few months of age.

2. periventricular heterotopia

In this case, the problem is due to an alteration at the start of the migration. This affects a small group of neurons which accumulate in locations other than those that normally correspond to them.

In these cases, the person experiences strong seizures that emerge during adolescence. In addition, although they usually present normal intelligence, certain patients experience learning problems.

3. polymicrogyria

In polymicrogyria, the arrangement of the neural mass creates small abnormal gyri that are separated by shallow sulci, creating an irregular cortical surface.

In this condition, two types of polymicrogyria with different clinical pictures can be distinguished:

• Unilateral polymicrogyria: It manifests itself through irregularities in the visual field, focal seizures, hemiparesis and cognitive disorders.
• Bilateral polymicrogyria: this malformation occurs more commonly and is related to a large number of symptoms and pictures such as bilateral frontoparietal polymicrogyria or bilateral perisylvian syndrome congenital.

4. schizencephaly

Schissencephaly is distinguished by presenting a normal volume of Gray matter but with alterations in the gyri of smaller size and more superficial than usual and surrounded by grooves of very little depth.

This pathology does not have specific clinical symptoms, but these can vary according to the extension and location of the affected areas. In some cases, visible clinical pictures may not manifest, while in others people may suffer epileptic episodes of variable intensity.

5. other

Other neurological disorders that originate from an alteration in neuronal migration are:

• Subcortical band heterotropia.
• Holoprosencephaly.
• colpocephaly.
• Porencephaly.
• Hydranencephaly.