Vertebrate sensory perception and integration depend on the formation of ordered connections between sensory neurons and their target cells that occur along several steps: a- establishment of cellular identity, b- neuronal axon growth, arborization and dendritogenesis, c- somatodendritic contact and synaptic refinement. Although there is a wealth of information about the molecular mechanisms controlling neuronal cell-fate determination and synaptogenesis during embryonic development, very few studies have analyzed the long-term dynamics of sensorineural circuitry in adult animals. We are employing the zebrafish lateral-line system to understand the mechanisms that govern the formation, homeostasis and regeneration of a mechanosensory organ. We have obtained evidence that intrinsic and activity-dependent mechanisms cooperate during the elaboration and refinement of the organ’s innervation. The goal of this research proposal is twofold: to characterize the mechanisms of sensorineural dendritic elaboration and remodeling, and to analyze how sensory organs reinnervate to recover function after damage. The first aim is to perform an exhaustive analysis of the cellular and molecular events leading to the formation of neuronal topography and the kinetics of target recognition. The second aim is to characterize the contribution of sensory function to dendrite arborization, asking whether epigenetic mechanisms shape sensorineural synaptic fields in the periphery. Finally we shall analyze how the architecture of the sensory epithelium relates to dendrite arborization. Achieving these goals will help us understand how animals maintain sensory abilities throughout their entire lives. It may also provide a framework for the development of strategies of regenerative medicine aimed at ameliorating the negative effects of age-related loss of sensory function, peripheral neuropathies, or cerebral stroke in humans.
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