Comparative behavioral genetics: the Yamamoto approach

This special issue of the Journal of Neurogenetics celebrates the achievements and unique contributions of Daisuke Yamamoto on the occasion of his lab relocation from Tohoku University, where he spent nearly 13 years (2005–2018). Daisuke’s profound and persistent scientific interest is sexual behavior of insects, Drosophila melanogaster in particular. His characteristic strategy amply illustrated an effective multi-layered approach: identification of genes and neural circuits that shape or control behavior and how they adapt and contribute to mating behaviors in different species. We here call this unique approach “comparative behavioral genetics.”

We would like to briefly highlight some landmark successes of this approach. As a project leader at the Mitsubishi Kasei Institute of Life Sciences, Daisuke started Drosophila research with a heroic mutant screen for altered sexual behavior. It was 1988, and he was much influenced by a series of astonishing successes in isolation of behavioral mutants by Seymour Benzer. Daisuke’s goal of this behavioral screen was to identify genes responsible for the behavioral mutants. He materialized it with a bounty harvest of many genes – one of the most famous examples is the cloning of the fruitless gene, via the homosexual mutant he named satori (Ito et al., 1996; see also cover photo). Needless to say, fruitless is central to controlling sexual behavior in male Drosophila melanogaster through the male-specific expression of the functional Fruitless protein product following sexually dimorphic splicing (Ryner et al., 1996; Yamamoto & Koganezawa, 2013).

In collaboration with Ken-ichi Kimura, Daisuke made an unexpected discovery on marked sexual dimorphism in the number and morphology of fruitless-expressing neurons in the brain (Kimura, Ote, Tazawa, & Yamamoto, 2005). It was published in 2005, the year when he moved to Tohoku University. By then, it was generally assumed that altered sexual behavior in fruitless mutants arose solely from expression of the male form of the Fruitless protein without neural circuit modification. However, Daisuke’s discovery revealed that this misconception largely arose from a lack of technical resolution. By applying the clonal analysis to fruitless-expressing neuronal clusters, Kimura and colleagues delineated Fruitless-dependent sex-specific neuronal differentiation (Kimura et al., 2005). While the clonal analysis is widely accepted as an experimental approach of choice to label single cells in the brain (and any other tissues; Lee & Luo, 1999), experiments and data acquisition are nevertheless often very laborious, because target cell labeling is stochastic. To the surprise of the community, the stamina of the Yamamoto group perfected this approach to reliably target transgene expression or mutation of interest to small populations of neurons, which made further measured functional consequences in behavioral assays possible (Ito et al., 2016; Kimura, Hachiya, Koganezawa, Tazawa, & Yamamoto, 2008; Kimura et al., 2015; Koganezawa, Haba, Matsuo, & Yamamoto, 2010; Kohatsu, Koganezawa, & Yamamoto, 2011; Kohatsu & Yamamoto, 2015; Sakurai, Koganezawa, Yasunaga, Emoto, & Yamamoto, 2013). This apparently “crazy” and challenging approach has not been repeated by many groups, and therefore became an iconic trademark of his team.

Guided by his deep interest in evolution, Daisuke combines this unique behavioral genetics approach with his long and strong track record on comparative studies with a diversity of Drosophila species beyond D. melanogaster, particularly a richly diversified Hawaiian species. His scientific curiosity in evolution apparently has rooted from his childhood, where he spent days catching insects. Systematic collection of local butterflies and moths made this young budding scientist recognize small, but clear, speciation distinctions, and left him wondering how these morphological and behavioral distinctions could come about. His excitement in local speciation should have driven him, decades later at Tohoku University, to produce a series of innovative studies with D. subobscura that shows strikingly unique courtship behavior (Higuchi, Kohatsu, & Yamamoto, 2017; Takayanagi et al., 2015; Tanaka, Murakami, Ote, & Yamamoto, 2016; Tanaka, Higuchi, Kohatsu, Sato, & Yamamoto, 2017).

We are delighted to see this Yamamoto spirit permeating in the nine articles contributing to this special issue. The lead authors of these contributors are former members of the Yamamoto lab (Yuki Ishikawa, Yoshiro Nakano, and Ken-ichi Kimura) and collaborators/friends (Chun-Fang Wu, Jean-François Ferveur, Nobuhiro Yamagata, Nicolas Gompel, Ya-hui Chou, and Shu Kondo).

The groups of Shu Kondo and Ya-Hui Chou report new genetic resources with their pitfalls. Kondo and colleagues developed a method to monitor activation of an endogenous receptor by inserting the TANGO reporter to the C-terminal of a GPCR (Katow, Takahashi, Saito, Tanimoto, & Kondo, 2019). The Chou group presents a genetic resource for labeling local interneurons in the antennal lobes, reporting technical pitfalls in in-vivo transgene swapping (Chen et al., 2019).

Yuki Ishikawa and colleagues report species-selective locomotion changes upon auditory stimulation (Ishikawa et al., 2019). They have characterized parameters of courtship songs that influence walking patterns of D. melanogaster and compared them with those of D. sechellia and D. simulans (Ishikawa, Okamoto, Yoneyama, Maeda, & Kamikouchi, 2019). Nicolas Gompel and colleagues summarized recent advances on oviposition of insects including Drosophila. It provides a nice read of a comprehensive review on neural circuits that control when, where and how insects lay eggs (Cury, Prud’homme, & Gompel, 2019).

In highlighting the pleiotropy of the mutations that affect sexual behavior, we have another review article contributed by Yoshiro Nakano about the lysosomal protein Spinster and its diverse functions including female receptivity (Nakano, 2019). Pleiotropy is also well illustrated in the article led by Jean-François Ferveur. They show the case with the desaturase 1 gene in different cell types (Nojima et al., 2019). Furthermore, Kimura, Urusizaki, Sato, and Yamamoto (2019) demonstrate sexual dimorphism of pheromone sensing neurons in the legs using the clonal analysis.

Finally, the group of Chun-Fang Wu made comprehensive electrophysiological characterization of stimulations that recruit distinct types of motor pattern generator activities, including seizure (Lee, Iyengar, & Wu, 2019). Nobuhiro Yamagata and colleagues report increased sexual activity upon presenting a previously rewarded odor (Onodera, Ichikawa, Terao, Tanimoto, & Yamagata, 2019).

It is noteworthy that none of these articles are biographical recollection, but mostly original research papers, perhaps reflecting our curiosity of Daisuke’s continued new science in the Advanced ICT Research Institute in the years to come. To culminate this special issue in honor of Daisuke Yamamoto, we provide a photo gallery, illustrating his love beyond science: food, travel, and his wife Sumiko. A couple of photos document his lab at Tohoku University after the Great East Japan Earthquake in 2011, highlighting the survival, revival, and regrowth of Daisuke’s team.

Acknowledgments

HT: I am very honored to be a colleague of Daisuke Yamamoto. He not only helped us setting up my new lab at the Tohoku University in 2013, but guided me and my lab members to adapt to the academic and administrative systems that were alien to us at that time. Retrospectively, it was truly fortunate that Daisuke and his team with international perspectives were the closest colleague of us. CFW: I am privileged to have been close friends with Daisuke Yamamoto since our post-doctoral days. Although our research diverged, we have maintained close contact, and, with growing admiration, I am confident that the best of Yamamoto’s triumphs is still to come.

Disclosure statement

No potential conflict of interest was reported by the authors.