Cellular and molecular control of progenitor migration in early cranial sensory ganglion formation

The principal components of the sensory nervous system are the neurons which convey sensory information such as touch, taste, sound from receptors in the body to the central nervous system (cns) for processing. The cell bodies of the neurons are found grouped together in structures termed ganglia while long cellular projections (axons) extend out into the periphery of the body, and into the cns. The neurons are born from migratory progenitors which are generated at a distance from the site of the sensory ganglia and must migrate within the developing embryo to form the ganglia. Our research focuses on one particular group of sensory ganglia in the head called the epibranchial ganglia. These ganglia are important because they relay sensory information relating to CO2 levels and blood pressure from blood vessels as well as taste from the mouth. The sensory neuron progenitors of these ganglia are born in specialized regions of the surface ectoderm of the head called neurogenic placodes. Once they have been generated the progenitors must leave the placode and migrate internally to form the ganglia. Since little is known about the migration of these progenitors the research outlined in this proposal aims to gain further insight into the mechanisms that control the process of their migration. One way we aim to do this is to visualise the process as it happens in the embryo. We can do this by introducing fluorescent labels into the progenitors and using timelapse videomicroscopy to follow the fluorescent cells as they migrate in real time in cultured embryos. This will give us information about the dynamics of the process which will allow us to make predictions about the mechanisms underlying it. We know from previous studies that when a separate population of cells called neural crest cells are missing from the embryo, the epibranchial sensory ganglia do not form correctly. We want to test whether there is a physical interaction between the neuronal progenitors and the neural crest cells that facilitates the migration of the progenitors to form the ganglia. We intend to use an inducible system to remove the neural crest cells at a particular time during progenitor migration, and to determine the effects on the process. We will also determine whether these neural crest cells act to guide the direction of progenitor migration by having neural crest cells where they would not normally be and seeing whether the neuronal progenitors follow. This research will elucidate the mechanisms underlying the process of neuronal progenitor migration in the formation of these functionally important sensory ganglia. This will be of intrinsic interest in the development of the sensory nervous system, as well as being tremendously informative for the wider field of cell migration in the developing embryo.

The sensory nervous system in the head differs markedly from that of the trunk, being derived from two distinct embryonic tissues: neural crest and neurogenic placodes. Our research focuses on the development of the distal ganglia of cranial nerves VII, IX and X. Termed collectively the epibranchial ganglia they contain sensory neurons important in the processing of sensory information relating to taste, as well as chemoreception and pressure reception in the blood vessels. The sensory neuron progenitors are born in specialized regions of surface ectoderm, the epibranchial neurogenic placodes. The progenitors must then leave the epithelium and migrate internally to the site of ganglion formation, yet little is known about the mechanisms by which this occurs. It has long been assumed that the placodal progenitors use the same mechanism as neural crest cells to migrate. However our recent studies argue against this as the progenitors leave the epithelium with a neuronal morphology rather than the neural crest mesenchymal morphology. This also means that the migration is distinct from the best described system of placodal progenitor migration namely the lateral line where the whole primordium migrates. Thus, the migration of epibranchial neuronal progenitors occurs via a novel mechanism. The aim of the research outlined in this proposal is to gain further insight into the mechanisms driving this migration process. We will use a study of dynamic changes in cellular morphology during progenitor migration to predict potential mechanisms. We will test the role of an interaction with neural crest cells that facilitates the migration of placodal progenitors and determine additional guidance roles. This will be of intrinsic interest in the development of these sensory ganglia, yet will also be tremendously informative for the wider field of cell migration in the developing embryo.