Despite the functional importance of the motor neurons that innervate the head and neck, the mechanisms regulating their development are still not well understood. In particular, the specification of motor neuron subtype identity withina single segment of the brain (rather than between different segments of the brain) in an unexplored area. The vagus motor neurons are a particularly interesting population because the cell bodies are contained in a single segment of the vertebrate hindbrain, called rhombomere 8, but peripherally the axons are highly segmented into five separate branches. In preliminary experiments using zebrafish as a model of vertebrate hindbrain development, I show that the vagus motor neurons are regionalized in the brain in a way that reflects the segmentation of their axons, such that multiple vagus motor neuron subtypes are present within rhombomere 8. This system therefore allows us to ask how motor neuron subtype identity is specified within a single segment of the hindbrain. Furthermore, it has been shown that vagus motor neurons, which in humans innervate the muscles of the larynx and pharynx, are abnormal in DiGeorge Syndrome, the most common microdeletion syndrome in humans. This proposal investigates how motor neuron subtype identity is affected in a zebrafish model of DiGeorge Syndrome. This has the potential to explain why patients DiGeorge Syndrome experience dysphagia, an important clinical problem whose mechanistic basis is unknown.
DiGeorge Syndrome is one of the most common human genetic disorders, yet the mechanisms underlying the neurologic symptoms of the disorder are not well understood. This proposal investigates the fundamental developmental progression of the neurons affected in DiGeorge Syndrome, and determines how those neurons are altered in a zebrafish model of DiGeorge Syndrome.
|Barsh, Gabrielle R; Isabella, Adam J; Moens, Cecilia B (2017) Vagus Motor Neuron Topographic Map Determined by Parallel Mechanisms of hox5 Expression and Time of Axon Initiation. Curr Biol 27:3812-3825.e3|