Research

Instinct is organized by genetic programs that preconfigure the appropriate neural circuitry. Genetic dissection in model organisms thus has the potential to reveal the molecules, neurons, and circuits underlying such behaviors, allowing us to determine the principle for instinct. With this goal in mind, I am studying the male courtship ritual of Drosophila melanogaster.

This instinctive behavior is specified during development by the male-specific products of the fruitless (fru) gene, Fru, which are expressed in ~ 2000 cells in the male CNS (Usui-Aoki et al., Nat Cell Biol, 2000). The fru mutant males show enhanced intermale (male-to-male) courtship, with a concomitant decline in the activity to court to and copulate with females (Ito et al., PNAS, 1996). The enhanced homosexual courtship in fru mutant males is considered to result from de-masculinization of a part of the brain due to loss-of-function of the fru gene. In fact, some fru-expressing neurons, such as those in the mAL and P1 clusters, are sexually dimorphic in their number and projections. These neurons are completely feminized in males who are loss-of-function fru mutants (Kimura et al., Nature, 2005; Kimura et al., Neuron, 2008). Conversely, ectopic activation of fru in the female brain is sufficient to induce male courtship behavior. Therefore, fru is proposed to act as a master control gene that confers the male identity on the brain that generates male courtship behavior. fru encodes putative transcription factors with Zn-finger (DNA-binding) and BTB (protein-protein interaction) motifs (Ito et al., PNAS, 1996).

Despite of extensive analyses of the fru gene, it is not well understood how Fru produces sexually different neural circuitry required for proper recognition of sexual partners. To elucidate its molecular and cellular mechanisms of actions of fru, I attempted to identify the genes interacting with fru. I have gotten the evidence that the fru gene genetically and physically interacts with longitudinal lacking (lola), a multifaceted regulator of axon guidance, suggesting the possible mechanism whereby Fru controls transcription of a large set of genes for neural sexual differentiation (Sato et al., Nat Communs, 2019).