The early developmental gene Semaphorin 5c contributes to olfactory behavior in adult Drosophila

Behaviors are complex traits influenced by multiple pleiotropic genes. Understanding the mechanisms that give rise to complex behaviors requires an understanding of how variation in transcriptional regulation shapes nervous system development and how variation in brain Structure influences all organism's ability to respond to its environment. To begin to address this problem, we used olfactory behavior ill Drosophila melanogaster as a model and showed that a hypomorphic transposon-mediated mutation of file early developmental gene Semaphorin-5c (Sema-5c) results in aberrant behavioral responses to tile repellant odorant benzaldehyde. We fine mapped this effect to the Sema-5c locus using deficiency mapping, phenotypic reversion through P-element excision, and transgenic rescue. Morphometric analysis of this Sema-5c allele reveals subtle neuroanatomical changes in the brain with a reduction in the size of the ellipsoid body. High-density oligonucleotide expression microarrays identified 50 probe sets with altered transcriptional regulation in the Sema-5c background and quantitative Complementation tests identified epistatic interactions between nine of these coregulated genes and the transposon-disrupted Sema-5c gene. Our results demonstrate how hypomorphic mutation of all early developmental gene results in genome-wide transcriptional consequences and alterations in brain structure accompanied by profound impairment of adult behavior.