MOLECULAR GENETICS OF SENSORY GANGLIA DEVELOPMENT

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DESCRIPTION (provided by applicant): The sensory ganglia of the peripheral nervous system provide information about the environment to the central nervous system. The long-range goal of our research is to determine how sensory ganglia develop. The main focus will be on the trigeminal sensory ganglia, an assembly of neurons in the vertebrate head that mediate touch, temperature and pain sensations. Injuries and malformations of the trigeminal nerve are clinically and cosmetically devastating and are often associated with trigeminal neuralgia, a severe and recurrent neuropathic facial pain syndrome. Despite its important role, it is still poorly understood how the trigeminal ganglion develops. Using zebrafish as a model system, the earliest steps of trigeminal ganglion development will be analyzed by combining in vivo imaging of fluorescently labeled neurons and axons with embryological and genetic manipulations. Specific Aim 1 will determine how the ganglion is assembled from neuronal precursors. We will test the hypothesis that short-range chemokine signaling and neuron-neuron interactions regulate the location and clustering of trigeminal ganglion neurons. Specific Aim 2 will examine how the peripheral axons of the trigeminal ganglion come to cover and partition the receptive area of the head epidermis. We will determine how axon-axon interactions determine the direction of axon outgrowth and sculpt the axon arborization pattern of the trigeminal ganglion. The role and interaction of guidance signals in trigeminal ganglion assembly and axon arborization will be analyzed. These studies will contribute to our understanding of ganglion development and provide insights into the mechanisms through which neurons assemble and partition receptive areas, two fundamental issues in developmental neurobiology.