The formation of the neural tube from a flat sheet of ectoderm is called neurulation. The initially simple tube will develop and form the brain, spinal cord and retina, and is the source of neural crest cells and their derivatives.
As cells of the epiblast pass through the primitive streak during gastrulation, some of those cells are destined to form a distinct col- lection of cells in the midline of the developing embryo.
The primitive node extends as a tube of mesenchymal cells running in the midline of the embryo between the ectoderm and endoderm. This is the notochordal process. It grows and extends in a cranial direction developing a lumen.
Around day 20 the notochordal process fuses with the endoderm beneath it, forming the notochordal plate. A couple of days later the cells of the notochordal plate lift from the endoderm and form a solid rod, again running almost the full length of the midline of the embryo. This is the notochord (Figure 17.1).
The notochord is a signalling centre that signals to the cells of the overlying ectoderm. As the notochord forms the ectoderm in the midline of the embryo thickens, becoming the neural plate from day 18 (Figure 17.2). Now the ectoderm is becoming neuroectoderm. This begins at the cranial end of the embryo and extends towards the caudal end.
The neural plate is broader cranially, and this will form the brain. The remainder of the neural plate elongates and develops into the spinal cord.
The neural plate dips inwards in the midline, beginning to fold and form a neural groove (Figure 17.3). The sides of the groove are the neural folds, and the parts of neuroectoderm brought towards one another to meet are the neural crests. The neural crests look like the crests of two waves crashing into each other to complete the tube.
The two sides of the neural plate are brought together, meet and fuse, forming a self‐contained tube of neuroectoderm running the length of the embryo, open at either end (Figure 17.4). This is the neural tube.
The neural tube separates from the ectoderm, which reforms over the neural tube, forming the external surface of the embryo (Figure 17.5).
Development of the neural tube from the neural plate extends cranially and caudally, leaving either end open at the cranial and caudal neuropores (Figure 17.6). The cranial neuropore closes on day 24 and the caudal neuropore closes on day 26. Neurulation is now complete.
As the neural tube forms from the neural plate a new cell type appears in the neural crest. These are neural crest cells (Figure 17.4), and as the neural tube forms these cells leave the neural tube and migrate away to other parts of the embryo (Figure 17.5). They become parts of a wide range of organs and structures, and differentiate to form a variety of different cell types.
For example, they will form much of the peripheral nervous system, skeletal parts of the face and pigment cells in the skin (melanocytes). Migration and differentiation of these cells is well organised and an important part of the normal development of much of the embryo.
From neurulation the central nervous system continues to develop as the cranial end of the neural tube dilates and folds to form spaces that will become the brain. The remainder of the neural tube, caudal to the first 4 somites, will become the spinal cord.
Cells of the walls of the tube differentiate and proliferate to become neurons, glial cells and macroglial cells, and the walls thicken. You can read about the development of the central nervous system in Chapter 44.
The most common congenital abnormalities of neurulation are neural tube defects. As the neuropores are the last parts of the neural tube to close, defects are most likely to occur at its cranial or caudal ends.
Failure of the neural tube to close caudally affects the spinal cord and the tissues that overlie it, including the meninges, vertebral bones, muscles and skin.
Spina bifida (from the Latin for ‘split spine’) is a condition in which vertebrae fail to form completely. It may manifest in different degrees of severity. Spina bifida occulta is the least severe form with a small gap in one or more vertebrae in the region of L5–S1 (Figure 17.7), often causing little or no symptoms. An unusual tuft of hair may be present in this region of the back.
Spina bifida meningocoele is a failure of vertebrae to fuse that is large enough to allow the protrusion of the meninges of the spinal cord externally (Figure 17.7). If the spinal cord or nerve roots also protrude this is called spina bifida with meningomyelcoele. This may affect sensory and motor innervation at the level of the lesion, potentially affecting bladder and anal continence.
The neural tube may also fail to close at the cranial end, causing abnormal brain and calvarial bone development. The brain may be partly outside the skull (exencephaly) or the forebrain may fail to develop entirely (anencephaly). Exencephaly may precede anencephaly as the extruded brain tissue degenerates. Anencephaly is incompatible with life.
The incidence of neural tube defects is reduced by folic acid supplements in the diet, but as neurulation occurs during the third and fourth weeks it shou d early in pregnancy or when trying to conceive.