Short title: Shaping the head
Long title: Neural crest cells in development and disease
Most of the head skeleton arises from specialized cells that develop from the neural crest, a region of the embryo that forms at the edges of the neural plate. These cells are unusually multi-potent and extremely migratory, emerging from the neural plate to travel throughout the body. Once they arrive at their destination, they can form diverse tissue types such as neurons, connective tissue, and endocrine cells. In the head, they make up most of the cranial bone and cartilages. Structures such as teeth, jaws and sensory systems all receive contributions from the neural crest. Thus, the facial structures are intimately linked to this cell population. Species-specific differences in head structures are also thought to be due to variations in neural crest development.
Neural crest cells and congenital anomalies
Because the neural crest contributes substantially to the head structures, craniofacial anomalies can often be traced to changes in migration or differentiation of the neural crest cells. Shaping the head requires that many different kinds of tissues such as bones, muscles, nerves and skin all come together in the right place at the right time. Small changes in the embryo can lead to very big changes, sometimes with severe implications.
These processes are fascinating, and because they occur in three dimensions, are impossible to study in isolated cells. To study craniofacial anomalies, we use a variety of animal models: the mouse, which is the best genetic model of mammalian development, as well as frog and chick, which are great models for embryological manipulation of the neural crest. Our work on animal models of ciliopathies has recently uncovered a role for neural crest cells in high-arching palate, a common but little understood oral anomaly.
Neural crest cells: an embryonic “stem cell” population
One of the most intriguing characteristics of neural crest cells is their ability to differentiate into a prodigious variety of cell types. If this plasticity can be harnessed, neural crest stem cells could be useful later in life for repair and regeneration of many tissues. One of our major goals in the lab is to understand the signals regulating development decisions in the life of a neural crest cell. A long-term goal is to understand the genetic programmes underlying the plasticity of this cell population.
Neural crest cells migration: normal development and cancer
Neural crest cells travel long distances to reach their final destinations. Defects in neural crest cell migration can lead to problems throughout the body, causing diverse conditions such as heart anomalies, piebaldism and Hirschsprung’s disease, which is characterized by a lack of nerve supply to the gut. Furthermore, the multipotency of these cells, coupled with their migratory capabilities, make neural crest cells an important model for understanding tumorigenesis and metastasis. Indeed, neuroblastoma, which is thought to arise from the embryonic neural crest lineage, is the most common cancer in infants. Neuroblastoma is extremely aggressive, and the majority of cases are diagnosed after metastasis.
Clearly, studies on neural crest cells will lead us to a better understanding of the aetiology of a broad range of congenital anomalies. In addition, an understanding of the signals governing neural crest cell migration may provide insight into cancer metastasis and reveal new pathways for therapeutic intervention.