Laboratory/Faculty

Laboratory of Developmental Biology
Group of Animal Development

ProfessorYasuyoshi Nishida
Molecular mechanisms of Drosophila development
Associate ProfessorAkira Mizoguchi
Endocrine control of insect growth and development
Assistant ProfessorYoshimasa Yagi
Molecular mechanisms of innate immunity in Drosophila
Assistant ProfessorShin Sugiyama
Molecular mechanisms of Drosophila development
Laboratory HP
Japanese
Yasuyoshi Nishida Professor
Lab members

Formation of complex organisms from an ostensibly simple fertilized egg is one of the most fascinating phenomena in biology. We are trying to elucidate the molecular mechanisms involved in the regulation of proliferation, growth, differentiation and morphogenesis during animal development. For this purpose, we are using Drosophila melanogaster as a model organism: genetics, developmental biology and molecular biology are well developed in this species, and it is easy to analyze gene functions in intact flies by using well-developed techniques based on the unique characteristics of this organism.
Animals develop into organisms with fixed sizes and shapes within fixed time periods, all specific to each species. We are interested how the sizes of organs and organisms are determined. In order to understand this problem, it would be important to reveal how the mechanisms regulating cellular growth, proliferation, differentiation and apoptosis are coordinated.
We have isolated Drosophila mutants with severe growth defects. One hypomorphic mutant showed delayed growth and small body size; in this mutant, both cell size and number are reduced. Molecular cloning of the responsible gene revealed the primary structure of the protein, which contains a domain highly conserved throughout eukaryotes. The structure is similar to a component of the yeast mitochondrial protein translocator. Expression of HA-tagged cDNA in flies demonstrated the protein’s mitochondrial localization, suggesting that the Drosophila protein is an ortholog of the yeast protein. Overexpression of this gene is toxic and induces apoptosis. Suppression of apoptosis by co-expression of baculoviral p35, a caspase inhibitor, resulted in the upregulation of proliferation. These observations suggest the involvement of this gene in the regulation of cell growth, proliferation and apoptosis, as well as protein translocation. By screening the enhancers of the hypomorphic mutant, we are trying to identify the signaling cascade mediating the mitochondrial signals that regulate these processes. The hypomorphic mutant also showed defects in sperm morphogenesis. Interestingly, the Drosophila genome contains two related genes that are specifically expressed in the testis. We are currently analyzing their differentiated functions during sperm morphogenesis.
We have identified a new phosphatase gene similar to yeast Nem1, and are analyzing its functions during development. It is increasingly clear that the gene is a negative regulator of the BMP/Dpp signaling pathway, which is involved in diverse developmental processes such as sperm and oocyte differentiation and wing pattern formation.
We are also working on the molecular mechanisms of the innate immunity mediated by the Toll family receptors, the functions of myosin phosphatase during development, and the transcriptional regulation of neurogenesis in Drosophila.

We also investigate the endocrine mechanisms that regulate growth and development of insects, paying special attention to the roles of peptide hormones secreted by the central nervous system. The main themes of our research are the elucidation of 1) the roles of prothoracicotropic hormone (PTTH) and some other neuropeptides in the regulation of prothoracic gland activity, 2) the molecular and endocrine mechanisms underlying photoperiodic induction of pupal diapause and its termination, 3) the physiological functions of an insulin-like and an IGF-like peptide of insects.

References

  1. Mitonaka, T., Muramatsu, Y., Sugiyama, S., Mizuno, T. and Nishida, Y.: Dev. Biol. 309: 78-86 (2007)
  2. Sugiyama, S., Moritoh, S., Furukawa, Y., Mizuno, T., Lim, Y.-M., Tsuda, L. and Nishida, Y.: Genetics 176: 927-936 (2007)
  3. Yamasaki, Y. and Nishida, Y.: Develop. Growth Differ. 48: 411-418 (2006)
  4. Mizuno, T., Tsutsui, K. and Nishida, Y.: Development 129: 1215-1223 (2002)
  5. Yamanaka, N., Hua, Y. -J., Roller, L., Spalovska-Valachova, I., Mizoguchi, A., Kataoka, H., Tanaka, Y. (2010) Proc. Natl. Acad. Sci. USA 107: 2060-2065.
  6. Okamoto, N., Yamanaka, N., Yagi, Y., Nishida, Y., Kataoka, H., O’Connor, M. B., Mizoguchi, A. (2009) Dev. Cell 17: 885-891.
  7. Okamoto, N., Yamanaka, N., Satake, H., Saegusa, H., Kataoka, H., Mizoguchi, A. (2009) FEBS J. 276: 1221-1232.
  8. Yamanaka, N., Zitnan, D., Kim, Y. -J., Hua, Y. -J., Suzuki, Y., Suzuki, M., Suzuki, A., Satake, H., Mizoguchi, A., Asaoka, K., Tanaka, Y. and Kataoka, H. (2006) Proc. Natl. Acad. Sci. USA 103: 8622-8627.

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