Neurulation
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.
