Investigations are proposed to learn mechanisms that underlie the development of specific neurons and their connections in the CNS. The zebrafish, a vertebrate with marked advantages for developmental and genetic studies, will be utilized. The focus is on neurons that are segmentally arranged in the CNS, and that arise and begin to form their processes during the first day of embryogenesis. These neurons can be individually identified, in some cases before their processes grow, and examined in situ in the optically clear, small, and simply organized embryo. Specifically, (1) Lethal mutations will be obtained and the embryonic phenotypes the mutations produce will be studied, to identify genes that control CNS patterning and to characterize the roles of these genes during embryogenesis. (2) The relationships between development of brain segments and seginent-derived structures of the head periphery will be determined in normal and in experimentally perturbed embryos. These experiments may reveal whether brain segments are patterned as components of larger head metameres, and if head mesoderm is required for development of segmentation in the brain. (3) The relationships between brain segmentation and neuronal diversity in the brain will be examined by comparing the development of identified hindbrain reticulospinal neurons whose features vary according to the specific segments containing them. The origins of the dendrites of these neurons and of their early synaptic inputs will be determined. The studies will be carried out using antibodies to label the cells and newly forming synapses, and may also serve to identify molecules involved in synaptic target recognition.
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