Neurulation is the process by which the neural tube is formed during intrauterine development. The neural tube is fundamental for the differentiation of the cells of the central nervous system, while the neural crests, structures associated with it, are fundamental for the formation of the peripheral nervous system.

In this article we will describe the two phases of neurulation or neural tube formation : the primary phase, in which the neural plate begins to retract on itself, and the secondary phase, which culminates this process and allows the further development of the nervous system.

What is the neural tube?

The neural tube is an embryonic structure that forms during the first month of pregnancy; in particular, the tube has just closed around the 28th week after fertilization. It is the precursor of the central nervous system , composed of the brain and the spinal cord.

As embryonic development progresses, the neural tube is divided into four sections: the anterior (prosencephalon), mid (midbrain), posterior (hindbrain), and spinal cord. Each of these parts will progress to give rise to the different elements that make up the adult central nervous system.

While most of the nervous system develops from the walls of the neural tube , the gap between the walls – the neurocele or neural channel – is also relevant. This structure will be progressively transformed into the ventricles and the rest of the brain cavities, through which the cerebrospinal fluid circulates.

Primary Neurulation

After fertilization, the zygote is formed, the primary cell composed of the fusion of an egg and a sperm. The zygote divides successively, becoming a collection of cells called a morula. Later, the blastocele appears, a fluid-filled cavity within this structure; when this happens we speak of a “blastocyst”.

Later the blastula is divided into three layers: the endoderm, the mesoderm and the ectoderm . Each of these sections will give rise to different parts of the body. The ectoderm is the most important for the matter at hand, since the nervous system, both central and peripheral, develops from it.

The notochord, a structure located in the mesoderm, sends signals to the cells around it. Those that do not receive these signals are transformed into the neural plaque or neuroectoderm, a collection of cells that have already specialized in nerve functions. The word “plaque” refers to the flattened appearance of the neuroectoderm.

Primary neurulation consists of the proliferation of nerve cells in the neural plaque . These cause the plaque to be transformed into the neural tube, a fundamental step in the development of the human organism.

Neural tube formation and closure

During the process of neurulation the neural plate flattens, lengthens and folds over itself around the neural groove, which ends up having a U-shape as the walls rise, forming the neural crests and the neural tube . At this point in the process the tube is open at both ends; we refer to the caudal and rostral neuropores.

Normally, these openings close after a few days; however, sometimes the tube does not close properly , resulting in disorders such as spina bifida (affecting the spine) and anencephaly (associated with very serious malformations in the brain).

It is important to differentiate the neural tube from the neural crest because the former is transformed into most of the structures of the central nervous system, while the peripheral one is a progression of the neural crest.

Secondary neurulation

Secondary neurulation is the process that culminates the formation of the neural tube . This is not due to the signals sent by certain cells, as is the case with primary neurulation, but is the result of the development of the neural tube itself.

This process is associated with the division of neural tube cells into mesenchymal and epithelial cells. The former are located in the central part of the tube, and the latter in its peripheral region. As these cells differentiate, cavities are formed between the two sets.

The mesenchymal cells that are located in this part of the embryo condense and form what we know as the medullary cord; this, in turn, hollows out inside until it gives way to the neural tube cavity. This phenomenon begins in the sacral region of the spine .

Thus, while primary neurulation consists of the retreat of the neural plate onto itself, secondary neurulation corresponds to the emptying of the neural tube cavity, which is strongly associated with the differentiation of the cells of the embryo’s nervous system.