Mutations in the small optic lobes (sot) gene of Drosophila melanogaster cause specific cells to degenerate in the developing optic lobes, resulting in the absence of certain classes of columnar neurons. These neuronal defects lead to specific alterations in behavioral characteristics, particularly during flight and walking maneuvers The molecular mechanisms by which neurons die in either vertebrates or invertebrates are almost totally unknown. This applies to naturally programmed cell death as well as to neuronal degeneration caused by mutation (1-3). The demonstration by Miller and Benzer (4) that nearly 50% of the monoclonal antibodies made to the adult Drosophila brain cross react specifically to the human brain and the increasing number of genes that are found to be homologous between flies and humans mean that a molecular genetic analysis of neuronal degeneration in Drosophila may provide insights into basic mechanisms of nervous system development and into some human brain diseases. Furthermore, mutations in such genes that give rise to behavioral changes as a result of specific alterations in neuronal circuitry are particularly interesting in that they allow the identification of neuronal circuits that underpin the behavioral repertoires of an organism (3, 5-7). One such gene is small optic lobes (sob), which, when mutated, produces a specific defect in the adult nervous system as the result of neurodegeneration. This cell death is correlated with certain behavioral changes. The molecular cloning of this gene, which we describe in this report, thus allows us in this instance to complete the link from molecules to neuronal circuitry and behavior.In contrast to the normal methodologies of mutant isolation, the pioneering work of Heisenberg and Bohl (8) used a histological method to isolate structural brain mutants using altered brain morphology as an assay. One such mutant from this type of screen was small optic lobes, in which cell degeneration in the pupal optic lobes leads to a nearly 50%6 reduction in the cell number of the neuropiles of the medulla, lobula, and lobula plate (9, 10). Among the missing neurons in adult flies are many columnar neurons-e.g., certain classes of transmedullary neurons that project to the lobula (Tm neurons) or to the lobula and lobula plate (TmY neurons) (10). However, it is important to note the specificity of the cell types involved in, as well as excluded from, the neurodegenerative processes. For example, the number of columns in a mutant medulla is normal, and the lamina and central brain appear unaffected. Thus we are basically dealing with a brain in which the number of cell types in each of the repetitive columns of the medulla and lobula complex has been reduced (7). These specific optic lobe defects leave some behaviors intact whereas others are altered. Thus the optomotor yaw response is qualitatively normal whereas visual behaviors concerning landing response and figure ground discrimination are abnormal (10).In this communication we report the mapping ...

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