CHAPTER 8 NEURULATION

NEURULATION is a fundamental event of embryogenesis. It leads to the formation of the neural tube,
the precursor of the Central Nervous System including the brain and spinal cord

- Formation of the Neural Tube: Primary and Secondary Neurulation -

Epiblast is induced to form NEURAL ECTODERM

PRIMARY NEURULATION: is the dorsal thickening in the anterior ectoderm concomitant with regression
of the primitive streak

- this elliptical region of specialized thickened ectoderm is referred to as the NEURAL PLATE

- neural plate undergoes SHAPING which converts it into more elongated key-hole structure with broad
anterior and narrow posterior

- neural plate shaping is followed by the development of two lateral elevations, the NEURAL FOLDS on
either side of a depressed midregion referred to as the NEURAL GROOVE

- the neural folds continue to elevate appose in the midline and eventually fuse to create the NEURAL
TUBE which becomes covered by the surface ectoderm that will develop into the future epidermis

- the primary neurulation creates the BRAIN and most of the SPINAL CORD

SECONDARY NEURULATION: it forms the neural tube of the tail bud

- this is different mechanism without a neural folding in which the spinal cord initially forms as a solid
mass of epithelial cells, and a central lumen develops secondarily by CAVITATION

*BENDING OF THE NEURAL PLATE AND APPOSITION OF NEURAL FOLDS

The bending of the neural plate, which is observed during primary neurulation occurs at three principal
sites:

Median Hinge Point (MHP)

Overlying the notochord

Paired dorsolateral hinge point (DLHP)

The MHP is induced by signals from the notochord and is the sole site of bending in the upper spinal
plate
*FUSION NEURAL TUBES

Fusion begins in the cervical region and proceeds anteriorly and posteriorly and it is mediated by cell
surface GLYCOCONJUGATES

As a result of these processes the neural tube is formed and separated from the overlying ectodermal
sheet.

Until fusion is complete the anterior and posterior ends of the neural tube communicate with the
amniotic cavity via two openings the anterior and posterior neuropores.

Closure of the neuropores completes the neurulation.

The anlage of the spinal cord and a much broader cephalic portion

The primordium of the ENCEPHALON.

*APOPTOSIS DURUNG NEURULATION

APOPTOSIS = CELL DEATH

During neurulation cell proliferation is also accompanied by some degree of apoptosis in the
neuroepthelium

Midline remodelling by apoptosis breaks the continuity between the neuroepithelium and surface
ectoderm

- Neural Crest -

*FORMATION OF THE NEURAL CREST

As the neural fold elevate cells of the lateral border or crest of the neuroepithelium, the neural crest
undergo an EPITHELIO-MESENCHYMAL TRANSITION as they leave the neuroectoderm by active
migration into the underlying mesoderm

Neural crest cells express slug a transcription factor of the zinc finger family that characterizes cells that
break away from an embryonic cell layer to migrate mesenchymal cells

*MIGRATION OF NEURAL CREST CELLS

Neural crest cells that leave the anterior parts of the neural folds before closure of the neural tube in
this region contribute to the craniofacial skeleton and other mesenchymal derivatives but can also
differentiate into several other cell types including neurons of the cranial ganglia Schwann Cells and
melanocytes

*ANTERIOR NEURAL CREST

The anterior neural crest is a major component of the developing cephalic end of the embryo.

The anterior neural crest is the major morphological substrate for the evolution of the vertebrate head.

Neural crest cells from Rhombomeres 1 and 2 migrate into the first pharyngeal arch form the bulk of its
mesenchyme

Neural crest cells of rhombomere 4 migrate into the second arch and those of rhombomeres 6 and 7
into the third arch

*CIRCUMPHARYNGEAL NEURAL CREST

The CIRCUMPHARYNGEAL NEURAL CREST arises in the posterior rhombencephalon region and in the
lower part of the larynx. Cells from this region migrate towards the gut

VAGAL NEURAL CREST CELLS migrate into the developing gut as precursor of the parasympathetic
muerons of the digestive tract

They migrate posteriorly until together with neural crest cells from the sacral region, they populate the
entire length of the gut. These cells form the submucosal and myenteric plexuses.

The cardiac neural crest cells contribute massively to the TRUNCOCONAL FOLDS that separate the
outflow tract of the heart into the aortic and pulmonary segments to the leaflets of the semilunar valves
at the base of the outflow tract and to the walls of the proximal CORONARY ARTERIES near their
attachment to the ascending aorta.

The cardiac neural crest cells can also differentiate into SCHWANN CELLS of the cranial nerves

Circumpharyngeal neural crest also migrate ventrally to the pharynx they accompany the somite derived
myoblast that are migrating anteriorly to form the intrinsic muscles of the tongue and hypopharyngeal
muscles.

-Trunk neural crest-

The trunk neural crest extends from the sixth somite to the most posterior somites.

three main migratory pathways of neural crest cells;

One is a dorsolateral pathway between the ectoderm and the somites. The cells that take this pathway
disperse beneath the ectoderm and ultimately enter it as pigment cells (melanocytes).

In the second ventromedial pathway, neural crest cells initially move into the space between the
somites and the neural tube in the anterior half of the embryo. Cells that use this branch belong to the
sympathoadrenal lineage and contribute to the sympathetic nervous system and to the adrenal medulla.

A third ventrolateral pathway goes into the anterior halves of the somites. Cells that follow this pathway
form the segmentally arranged sensory or spinal ganglia.

SYMPATHOADRENAL LINEAGE is derived from committed sympathoadrenal progenitor cells that have
already passed a number of restriction points so that they can no longer form sensory neurons, glia, or
melanocytes.

The bipotential progenitor cells already possess some neuronal traits, but final differentiation depends
on their environment.

Within the gut the neural crest cells form the enteric nervous system which, in many respects, acts like
an independent component of the nervous system

-Phylogenetic origin of the neural crest-

Phylogenetically, the neural crest is a typical vertebrate feature.

It is assumed that the neural crest arose as a result of the centralization of the nervous system seen in
vertebrates

neural crest cells have two basic developmental fates:

-they form the ganglionic elements and supporting structures of the peripheral nervous system

-they can differentiate into mesenchyme (ectomesenchyme).