S. Lawrence Zipursky

I have studied neural development using the fruit fly, Drosophila melanogaster, as a model. We have identified genes controlling different aspects neural development from early patterning genes regulating retinal specification, to genes regulating the formation of neural circuits. In more recent studies, we have used a combination of genetic and biochemical studies to uncover the function of a large family of cell surface proteins encoded by the Dscam1 locus in regulating neural circuit assembly in the fly nervous system. Dscam proteins are members of the immunoglobulin superfamily of cell recognition molecules. Through alternative splicing, the Dscam1 locus is predicted to encode 19,008 different extracellular domains or isoforms. These proteins exhibit isoform-specific homophilic binding; isoforms on one membrane bind selectively to the same isoform on an opposing membrane. Binding elicits a repulsive response. As each neuron expresses a unique Dscam1 signature, this family of proteins prevents inappropriate association between processes of the same cell. This "self avoidance" plays an essential role in patterning neural circuits throughout the fly nervous system.