Vertebrate axis formation

During development, as the germ layers form, the ball of cells still retains its spherical shape.
However, animal bodies have lateral-medial (left-right), dorsal-ventral (back-belly), and anterior-
posterior (head-feet) axes. How are these established? In one of the most seminal experiments
ever to be carried out in developmental biology, Spemann and Mangold took dorsal cells from
one embryo and transplanted them into the belly region of another embryo. They found that the
transplanted embryo now had two notochords: one at the dorsal site from the original cells and
another at the transplanted site. This suggested that the dorsal cells were genetically
programmed to form the notochord and define the axis. Since then, researchers have identified
many genes that are responsible for axis formation. Mutations in these genes leads to the loss of
symmetry required for organism development. Animal bodies have externally visible symmetry.
However, the internal organs are not symmetric. For example, the heart is on the left side and
the liver on the right. The formation of the central left-right axis is an important process during
development. This internal asymmetry is established very early during development and involves
many genes. Research is still ongoing to fully understand the developmental implications of these
genes.

Figure 16.4D.116.4D.1: Vertebrate Axis Formation: Animal bodies have three axes for
symmetry:lateral-medial (left-right), dorsal-ventral (back-belly), and anterior-posterior (head-
feet).

Neural tube

In the developing chordate (including vertebrates), the neural tube is the embryo’s precursor to
the central nervous system, which comprises the brain and spinal cord. The neural groove
gradually deepens as the neural folds become elevated, and ultimately the folds meet and
coalesce in the middle line and convert the groove into a closed tube, the neural tube or neural
canal, the ectodermal wall of which forms the rudiment of the nervous system.
Figure 16.4D.116.4D.1: Neural Tube: Transverse section of half of a chick embryo of forty-
five hours’ incubation. The dorsal (back) surface of the embryo is toward the top of this page,
while the ventral (front) surface is toward the bottom. (Neural tube is in green. )

Primary and secondary neurulation

The neural tube develops in two ways: primary neurulation and secondary neurulation. Primary
neurulation divides the ectoderm into three cell types: the internally located neural tube, the
externally located epidermis, and the neural crest cells, which develop in the region between the
neural tube and epidermis but then migrate to new locations. Primary neurulation begins after
the neural plate forms. The edges of the neural plate start to thicken and lift upward, forming the
neural folds. The center of the neural plate remains grounded, allowing a U-shaped neural groove
to form. This neural groove sets the boundary between the right and left sides of the embryo.
The neural folds pinch in towards the midline of the embryo and fuse together to form the neural
tube. In secondary neurulation, the cells of the neural plate form a cord-like structure that
migrates inside the embryo and hollows to form the tube.
Figure 16.4D.116.4D.1: Neural Tube Formation: The central region of the ectoderm forms
the neural tube, which gives rise to the brain and the spinal cord.

Each organism uses primary and secondary neurulation to varying degrees. Neurulation in fish
proceeds only via the secondary form. In avian species the posterior regions of the tube develop
using secondary neurulation and the anterior regions develop by primary neurulation. In
mammals, secondary neurulation begins around the 35th somite. Mammalian neural tubes close
in the head in the opposite order that they close in the trunk. In the head, neural crest cells
migrate, the neural tube closes, and the overlying ectoderm closes. In the trunk, overlying
ectoderm closes, the neural tube closes and neural crest cells migrate.
Neural tube subdivisions

Four neural tube subdivisions eventually develop into distinct regions of the central nervous
system by the division of neuroepithelial cells: the prosencephalon, the mesencephalon, the
rhombencephalon and the spinal cord. The prosencephalon further goes on to develop into the
telencephalon (the forebrain or cerebrum) and the diencephalon (the optic vesicles and
hypothalamus). The mesencephalon develops into the midbrain. The rhombencephalon develops
into the metencephalon (the pons and cerebellum) and the myelencephalon (the medulla
oblongata).

For a short time, the neural tube is open both cranially and caudally. These openings, called
neuropores, close during the fourth week in the human. Improper closure of the neuropores can
result in neural tube defects such as anencephaly or spina bifida. The dorsal part of the neural
tube contains the alar plate, which is primarily associated with sensation. The ventral part of the
neural tube contains the basal plate, which is primarily associated with motor (i.e., muscle)
control.

Signaling molecules and other factors

The neural tube patterns along the dorsal-ventral axis establish defined compartments of neural
progenitor cells that lead to distinct classes of neurons. This patterning occurs early in
development and results from the activity of several secreted signaling molecules. Sonic
hedgehog (Shh) is a key player in patterning the ventral axis, while Bone morphogenic proteins
(Bmp) and Wnt family members play an important role in patterning the dorsal axis. Other factors
shown to provide positional information to the neural progenitor cells include Fibroblast growth
factors (FGF) and Retinoic Acid. Retinoic acid is required ventrally along with Shh to induce Pax6
and Olig2 during differentiation of motor neurons. Three main ventral cell types are established
during early neural tube development: the floor plate cells, which form at the ventral midline
during the neural fold stage; as well as the more dorsally located motor neurons and interneurons.
These cell types are specified by the secretion of Shh from the notochord (located ventrally to
the neural tube), and later from the floor plate cells. Shh acts as a morphogen, meaning that it
acts in a concentration-dependent manner to specify cell types as it moves further from its source.
The different combinations of expression of transcription factors along the dorsal-ventral axis of
the neural tube are responsible for creating the identity of the neuronal progenitor cells.