NEURULATION: CHARACTERISTICS, WHEN AND HOW IT OCCURS - GEOGRAFÍA - 2025

The neurulation is a fundamental phase in embryonic development in the neural tube, a structure that will lead to the brain and spinal cord (central nervous system) develops.

It occurs in all vertebrate embryos, although in certain species it goes through two different processes: primary and secondary neurulation. The neurulation process begins around the third or fourth week of embryonic development.

The development of our brain is mediated by genetic instructions, intercellular signals, and our interaction with the external world. Initially, this development consists of the establishment of a primal nervous system.

Thus, it begins with the generation of neurons from undifferentiated cells, the formation of main brain regions, and the migration of neurons from their places of creation to their final places. This will lay the groundwork for the subsequent creation of axonal pathways and establishment of synapses (connections).

The neurulation process

To understand the neurulation process it is necessary to know some fundamental previous steps in embryonic development.

Before the cells that are to become the brain and spinal cord appear, there are layers of primitive cells that are essential for the later development of the nervous system. These layers are formed during the so-called “gastrulation”, which, as Lewis Wolpert indicated in 1986:

Germ layers

During this delicate period, in which a single sheet of cells divides into the three primitive layers or germ layers:

- Ectoderm or outer layer: gives rise to the epidermis and related structures such as hair and nails, as well as the nervous system.

- Mesoderm or intermediate layer: from it the muscles, bones, circulatory system, and reproductive and excretory organs will appear.

- Endoderm or inner layer: it will give rise to the digestive system and the respiratory system.

The mesoderm and endoderm invaginate (fold over themselves), defining the midline and the anterior-posterior and dorsal-ventral axes. These axes are important because in each area of ​​the germ layers different events will happen.

Formation of the notochord

Gastrulation also has a key function, which is the formation of the notochord. It begins to emerge at 18 days of gestation, and consists of a defined cylinder of mesoderm cells that expand along the midline of the embryo.

The notochord is formed through cellular movements that occur during gastrulation. At first, a superficial slit is formed called the primitive pit, which lengthens until it constitutes the “primitive line”. From there the mesoderm invaginates and extends inward to form a cylinder.

The notochord establishes the midline of the embryo, which will result in both halves of the body being symmetrical. This structure also defines the position of the nervous system and is essential for posterior neural differentiation.

In this way, the neurulation process begins. The notochord begins to send inductive signals to the ectoderm (which is just above it) for a group of neuroectodermal cells to differentiate into nerve precursor cells. The latter are the ones that will be part of the central nervous system.

The part of the ectoderm that covers the notochord is defined as the “neural plate”. As neurulation progresses, the neural plate begins to thicken, accumulating cells. These cells are arranged in two chains on either side of the midline of the neural plate.

The latter begins to fold in the midline (adjacent to the notochord). This gives rise to the neural sulcus, approximately at 20 days of gestation, which is becoming more and more accentuated.

The part of the neural plate that is immediately above the notochord is called the "floor plate." Whereas, the posterior part of the protruding ends of the sulcus is known as the “neural crest”.

Neural tube formation

Little by little, the two protruding cell chains of the neural plate are bending, seeking to touch. This results in a cylinder called the neural tube. The neural tube closes and is completed at approximately 22 days of pregnancy.

The mesoderm next to the neural tube thickens, dividing into structures called "somites." These structures are the precursors of the musculature and the skeleton.

During neurulation, different parts of the neural tube will develop different structures in our body. These changes begin at 24 days of gestation. Thus:

- The part of the neural tube adjacent to the somites, begins to become the rudimentary spinal cord.

- The area of ​​the neural crest will give rise to the sensory ganglia of the peripheral nervous system.

- The anterior ends of the neural plate, called “anterior neural fold”, will expand together in the midline to originate the brain.

- The cavity of the neural tube will become the ventricular system.

Brain and spinal cord

Thus, the neural tube will give rise to the brain and the spinal cord. The cells of the neural tube are known as neural precursor cells, which are stem cells from which more precursors will emerge that give rise to neurons and glial cells.

On the other hand, some subsets of neural precursor cells do not divide. They are called neuroblasts, and they will differentiate into neurons.

While the cells of the ventral part of the neural tube (where the floor plate is) go to give rise to the spinal cord and the posterior part of the brain.

At 25 days' gestation, 3 basic vesicles can be seen that start from the neural tube: the forebrain, midbrain and rhombencephalon.

While, at 32 days, they are divided into 5 structures:

- The telencephalon: which gives rise to the cerebral cortex, the striatum, the limbic system and part of the hypothalamus.

- The diencephalon: which will develop the epithalamus, thalamus and hypothalamus.

- The midbrain: which will give rise to the tectum, tegmentum and cerebral peduncles.

- The metancephalon: which will differentiate into the cerebellum and the cerebral bridge.

- The myelencephalon: which will become the brainstem (medulla oblongata).

Primary and secondary neurulation

Primary and secondary neurulation are two fundamental phases in the neurulation process. In general, they define two types of neural tube formation.

The anterior part of it will be formed through primary neurulation and the posterior part, by secondary neurulation. Both occur at the same time, but in different places.

Each organism uses different degrees of primary and secondary neurulation; except fish, which use only the secondary.

Primary neurulation

Much of the neural tube develops during the third week of gestation from primary neurulation. Its formation extends to somite 31, which gives rise to the second sacral vertebra of the spine.

It begins when the cells of the neural plate begin to proliferate and to be located in two chains separated by an invagination in the midline.

Finally, the chains are bent and joined, constituting part of the neural tube. This part gives rise to almost the entire nervous system (brain, cervical, thoracic and lumbar spinal cord).

Secondary neurulation

The remainder of the neural tube is formed by secondary neurulation. It arises from the condensation, differentiation and degeneration of the mesenchymal cells that are in that area. (Chávez-Corral, López-Serna, Levario-Carrillo, & Sanín, 2013).

This occurs in the absence of the ectodermal germ layer or neural plate. It begins with the formation of a medullary cord by the condensation of mesenchymal cells, which hollows out to give rise to the neural tube.

This tube, also called the medullary tube, arises from an undifferentiated mass of cells called the causal eminence. Through morphogenetic mechanisms, they are organized to form a cavity to give rise to the spinal cord of the sacral and coccygeal region.

After secondary neurulation is complete, it joins the most caudal part of the primary neurulation.

Alterations in the neurulation process

It is possible that alterations may arise during neurulation due to genetic mutations or other reasons. Around 5 or 6 weeks of gestation, most of the brain and face begin to form. The hemispheres differentiate and the optic vesicles, the olfactory bulbs and the cerebellum grow.

If this important moment in neurodevelopment is altered, severe neurological and neuropsychological disorders usually appear. These are usually accompanied by seizures.

Alterations in this process lead to serious conditions. Especially if there are defects in the closure of the neural tube, which are not usually compatible with life. These occur between 1 in every 500 live births. The most common disorders that appear due to a bad closure of the neural tube are:

Anencephaly

It occurs due to poor closure in the anterior part of the neural tube during neurulation. It is characterized by the absence of some parts of the skull, brain and facial malformations, as well as heart problems.

Spina bifida

It arises from a neural tube defect that results in incomplete development of the brain, spinal cord, or meninges (protective layers that surround the central nervous system). There are several types of spina bifida: it can be a hidden malformation of one or more vertebrae, or a malformation of bones, membranes or fat in this area.

On the other hand, another subtype is the meningocele, in which the meninges protrude from the spinal opening, and may or may not be covered with skin.

Finally, the most serious subtype is myelomeningocele. In this case, the spinal cord is exposed and protrudes through the opening of the spine. This causes paralysis in the parts of the body that are below this opening.

Encephalocele

It is a sac-shaped lump in which the brain and meninges protrude through an opening at the level of the skull.

Cleft palate or cleft lip

It is a congenital defect that consists of a cleft or separation in the upper lip.

References

1. Chávez-Corral, D. V, López-Serna, N, Levario-Carrillo, M, & Sanín, LH (2013). Neural Tube Defects and Cleft Lip and Palate: a Morphological Study. International Journal of Morphology, 31 (4), 1301-1308.
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