The role of the neural crest in pharyngeal development
A key component of the pharyngeal arches is the neural crest. These will form and skeletal and connective tissue cells of the arches, the glia associated with the cranial nerves and the proximal sensory ganglia that reside alongside the hindbrain. A major aim of the lab is to understand the molecules that direct neural crest cells to follow these different fates – those that fill the arches becomes ectomesenchymal (that is form skeletal and connective tissues) while those that remain outside have a neuroglia fate. Signalling from the pharyngeal epithelia direct neural crest cells to become ectomesenhcymal and we have shown that this involves FGFs but it is clear that other signalling pathways are also required. We are therefore attempting to define these and uncover how they interact with FGF signalling. We are also attempting to define the molecules that guide neural crest cells along the neuroglial path in this region of the embryo and to understand how neural crest cells in this region of the body are directed to differentiate as sensory neurons. This is an important issue as it is clear that it involves mechanisms not used in the trunk, which is where this issue has been most extensively studied
The development of the sensory innervation of the pharynx
The majority of the sensory neurons that innervate the oropharyngeal region are derived from localised embryonic thickenings, termed neurogenic placodes. In the past we have shown that the neurogenic placodes associated with the pharyngeal arches develop as an integral part of that system. The pharyngeal endoderm, via the action of BMP signalling, plays an important role in the development of the placodes and the migration of cells from the placodes to the forming ganglia is guided by the neural crest cells that extend between the arches and the hindbrain. This has enabled us to build up a picture of how the cranial sensory ganglia are formed during development. We are currently analysing the development of the trigeminal system which supplied the sensory innervation for the derivative of the first pharyngeal arch and the facial prominences. This group of sensory neurons is particularly intriguing as these have complex developmental origins, arising from both neural crest and neurogenic placodes. We aim to understand how these two populations generate sensory neurons that contribute to this ganglion and how this may impinge on their later function.
Pharyngeal remodelling during development and evolution
Although the pharynx starts as a segmentally organised region, this territory becomes extensively remodelled during development. The second pharyngeal arch expands to cover the more posterior arches and encloses these which results in their obliteration. A major aim of the lab is to understand how the remodelling of the pharyngeal apparatus is directed. We have shown that SHH and thyroid hormone signalling is important here but we need to identify the other signalling pathways that direct this process and the molecules that effect the expansion of the second arch and its subsequent fusion with the underlying tissue. This study is not only important as it will inform us of this key even in pharyngeal development but it will also give us insights in the aetiology of branchial cleft and pouch anomalies which arise due to defects in this process, and these constitute the second most common developmental lesions of the head and neck in children. Finally, the remodelling of the pharynx is also an event that was associated with the evolution of the tetrapods and as such and understanding of how this occurs will further give us insights into this key event in early vertebrate evolution.