This special issue of Journal of Neurogenetics was born to honor the contribution of Yoshiki Hotta (b. 1938). Yoshiki is not only a major figure in the field of neurogenetics, but an influential leader for structuring Japanese academia and fostering young investigators—first as a faculty member at the University of Tokyo (1972–1998), then as the director general of the National Institute of Genetics (1997–2004), and finally as the president of the Research Organization of Information and Systems, until he stepped down in March 2011. At 73, one might consider this to be retirement. For those who know Yoshiki personally, such an interpretation does not seem valid (). Yoshiki himself has a plan for his next 50 years “with a spectrum different from science and administration.” We can therefore anticipate new excitements and stimulations emanating from Yoshiki, for many more years to come. Nonetheless, this seems to be an appropriate point to reflect on Yoshiki's contributions in science.
Figure 1. Yoshiki Hotta being introduced as an honorary guest speaker at the 1st Asia-Pacific Drosophila Research Conference (2011, Taipei).
Yoshiki Hotta initiated his scientific career as a medical student. After obtaining a medical degree in 1963, he joined the laboratory of Prof. Setsuro Ebashi in the Graduate School of Medicine, at the University of Tokyo. Ebashi was leading an active lab on muscle physiology; he had proposed the then-novel theory of how muscle contraction is regulated by calcium. Yoshiki, who wanted to study brain function, was somehow persuaded (tricked?) by Ebashi to work on the electrophysiology of smooth muscle contraction. This not only resulted in a first-author Nature paper and another Science paper (without coauthorship of his mentor), but also helped establish himself as a well-trained electrophysiologist.
Yoshiki maintained his strong interest in brain function, so when he heard that Seymour Benzer at the California Institute of Technology was starting a new field on “the genetics of behavior” using Drosophila and was looking for an electrophysiologist, he applied to the Benzer lab for a postdoctoral position. Benzer's initial idea was to use the phototactic behavior (normal flies run towards light) and isolate mutants with abnormal phototaxis, thereby identifying genes that are involved in this behavior. Only 1 year after joining the Benzer laboratory, Yoshiki was able to publish a paper showing that Drosophila mutants exhibiting abnormal phototactic behavior indeed have electrophysiological defects in their compound eyes.
The presence of a physiological defect in the eye does not necessary mean that the responsible gene acts in this tissue. Yoshiki and Benzer came up with a brilliant idea of using genetic mosaics to identify the site of gene action. They used the correlations between the behavioral phenotype and the genotype distribution of the cells throughout the organism to determine the anatomical foci where the responsible gene had to act, in order to produce a normal behavior. A remarkable feature of this method is that such critical information could be obtained without the knowledge of the gene product. In the following few years, Hotta and Benzer published a series of monumental works on the mapping of the foci of many behavioral mutants. These revolutionary and elegant works stimulated many people in and out of the lab. In this issue, two Benzer lab alumni, Bill Harris and Yuh-Nung Jan, kindly contributed essays on their interactions with Yoshiki.
After spending 4 years in California, Yoshiki came back to Japan in 1972 to set up his own laboratory in the Department of Physics at the University of Tokyo. Although it was quite unusual for someone who graduated from the School of Medicine to be hired as a faculty in the Department of Physics, Yoshiki's scientific talents and his broad interest and understanding of science matched well with this environment. In fact, Yoshiki's logical thinking and mechanistic approach to biology were perhaps more attractive to students with physical science background than to those with more traditional biological backgrounds. Yoshiki was quite successful in recruiting students from the Department of Physics as well as from the Department of Biochemistry, where he served as an adjunct professor. Many of his students went on to become successful independent researchers in diverse fields, and some of their recent achievements, as well as the influence that Yoshiki had on their career, are represented in this issue (Goto, Ueda, Sakai, Okamoto and Akiyama). The study of nonphototactic mutants that Yoshiki initiated with Benzer led to the discovery of the role of lipid metabolism in phototransduction (reviewed by Suzuki et al.). Isolation of flightless mutants, in combination of the two-dimensional gel electrophoresis analysis introduced to the Hotta lab (see essay by Fujita), led to the identification of major muscle proteins, as well as an unexpected involvement of a muscle protein actin in gene regulation. His laboratory also initiated genetic and molecular studies of the nervous system development. Major findings include identification of a molecular basis of synaptic specificity, and the identification of a “genetic switch” between neuronal and glial cell fate. Yoshihara and Ito review the current status of behavioral genetics, a field that Yoshiki helped initiate 40 years ago. In addition to research using Drosophila, Yoshiki took the initiative to start molecular neurogenetics of zebrafish in Japan; this topic is reviewed by Higashijima and Okamoto.
Besides activity as a researcher, Yoshiki made great efforts and contributions to offer young researchers greater opportunities to pursue independent research. In early 1990s, Yoshiki applied to and successfully won a large group grant on the genetic study of development. As the leader of the group, Yoshiki did not adopt the conventional route of distributing the money to the senior lab heads who control their groups with absolute authority, but rather directly funded the young emerging researchers. Many of the young researchers who received this grant became independent by the end of the grant period. His efforts gave a great impetus for the subsequent changes of the academic systems in Japan.
In 1997, Yoshiki left the University of Tokyo to assume the director general position of National Institute for Genetics (NIG). In 2004, he was elected as the president of the Research Organization of Information and Systems (ROIS), under whose umbrella NIG belongs. This move reflected Yoshiki's intention to actively participate in the large-scale improvement of the academic system in Japan. At ROIS he promoted interdisciplinary activities by creating the Transdisciplinary Research Integration Center, and helped disseminate the vast database to the entire scientific community by establishing the Database Center for Life Science. An essay by Sugimura and Uemura introduces some of these endeavors.
This special tribute for Yoshiki Hotta is unorthodox in that unlike many other tribute issues, we have not compiled numeral achievements he accomplished during his entire scientific career, but rather have put an emphasis on how Yoshiki implanted the seeds into the minds of individuals who had the great fortune of interacting with him, either as a student or colleague, and how the seeds were developed by them. Readers may be surprised to see the diversity in the courses that former students of Yoshiki have taken, but still how strongly they maintain a common spirit—which we would like to call “The Hotta Neurogenetics School.”