Neural Crest Cells
Neural crest cells
During
neurulation (see Chapter 17) a group of cells arises in the crests of the
neural plates that are brought together to form the neural tube (Figure 18.1).
These neural crest cells migrate out of and away from the neural tube to other
parts of the developing embryo. As they break cell contacts and leave the
neuroectoderm they become mesenchymal. The term mesenchyme typically refers to
the connective tissue of the embryo formed from the mesoderm. Neural crest
cells become histologically similar to the cells of the mesenchyme.
They
migrate, proliferate and differentiate into a number of different adult cell
types, contributing to many structures and organs, and you will find them
throughout this book. As they are able to differentiate into a number of
different cell types they are regarded as multipotent rather than pluripotent,
like many of the cells of the embryo at this stage.
The
migration of neural crest cells begins in the cranial end of the embryo shortly
before the neuropores of the neural tube close. Although they soon become
interspersed amongst the cells of the embryo that they are moving through, they
can be tracked in the lab with cell labelling techniques.
A cranial
group of neural crest cells migrates dorsolaterally to take part in formation
of structures of the head and neck. Two groups of trunk neural crest cells
migrate in different directions; either dorsolaterally around towards the
midline ectoderm (Figure 18.2) or ventrally around the neural tube and
notochord (Figure 18.3).
When
migrating neural crest cells encounter an obstacle that prevents further
progress they tend to clump and accumulate. An obstacle may be another group of
cells, a basal lamina or extracellular matrix molecules such as chondroitin
sulphaterich proteoglycans. A barrier to migration may cause the neural crest
cells to migrate along it in a particular direction. Other extracellular matrix
molecules such as fibronectin, proteoglycans and collagen will also affect the
migration of neural crest cells. By altering the localisation and concentration
of molecules that aid, encourage or inhibit migration the final location of
neural crest cells can be modified by the embryo.
Differentiation
of neural crest cells occurs in response to a range of external stimuli
encountered during migration.
Neural crest
cells taking the dorsolateral routes towards the ectoderm of the embryo will
differentiate into the melanocytes of the skin, for example. Some neural crest
cells in the trunk region that migrate ventrally will become neurons of the
dorsal root ganglia and sympathetic ganglia (see Chapters 39 and 45).
Neural crest
cell derivatives
•
Melanocytes (skin)
•
Dermis, some adipose tissue and smooth muscle of the neck and face (skin)
•
Neurons (dorsal root ganglia)
•
Neurons (sympathetic ganglia)
•
Neurons (ciliary ganglion)
•
Neurons (cranial sensory V, VII, maybe VIII, IX, X)
•
Schwann cells (nervous system)
•
Adrenomedullary cells (adrenal glands)
•
Enteric nervous system (gastrointestinal tract, parasympathetic nervous
system)
•
Craniofacial cartilage and bones (musculoskeletal)
•
Bones of the middle ear (musculoskeletal)
•
Thymus (immune system)
•
Odontoblasts (teeth)
•
Conotruncal septum (heart)
•
Semilunar valves (heart)
•
Connective tissue and smooth muscle of the great arteries (aorta,
pulmonary trunk)
•
Neuroglial cells (central nervous system)
•
Parafollicular cells (thyroid gland)
•
Glomus type I cells (carotid body)
•
Connective tissue of various glands (salivary, thymus, thyroid,
pituitary, lacrimal glands)
•
Corneal endothelium, stroma (eye)
Clinical relevance
Neural crest
cells are obviously important in various areas of embryological development,
and they must migrate in a very organised manner to complete this development
normally.
Sometimes,
neural crest cells do not migrate to their intended destinations. For example,
a deficiency in the number of neural crest cells available to form mesenchyme
in the developing face can cause cleft lip and cleft palate.
Albinism may be caused by a
failure of neural crest cell migration but is more likely to be caused by a
defect in the melanin production mechanism. However, pigmentation anomalies are
apparent in patients with Waardenburg syndrome, such as eyes of
different colours, a patch of white hair or patches of hypopigmentation of
skin. Waardenburg syndrome is associated with an increased risk of hearing
loss, facial features such as a broad, high nasal root and cleft lip or palate.
Gene mutations of one of at least four genes can cause Waardenburg syndrome,
including Pax3, a gene involved in controlling neural crest cell
differentiation.
An
abnormality of migration of neural crest cells into the pharyngeal arches can
lead to improper development of the parathyroid glands, thymus, facial
skeleton, heart, aorta and pulmonary trunk. This is 22q11.2 deletion syndrome
or DiGeorge syndrome (also known as CATCH22 syndrome). Congenital
defects vary between patients with DiGeorge syndrome but it is likely that they
will suffer hypocalcaemia, a cleft palate, a conotruncal defect such as a
ventricular septal defect or tetralogy of Fallot, recurrent infections, renal
problems and learning difficulties. These varied structures are linked by their
development from neural crest cells and pharyngeal arches.
