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)
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.