Outline of Research and Education

The processes of animal development, including organ size and body size, are genetically predetermined, but these processes are also influenced by environmental factors such as nutrition and temperature. The close link between cell and tissue growth control and environmental cues ensures that developmental transitions occur at the appropriate times during animal development. Our lab’s research aims to shed light on the molecular basis for growth control and developmental timing at the cellular and tissue/organ level using the fruit fly Drosophila melanogaster and mammalian cell culture as model systems. We combine biochemical and genetic approaches, along with quantitative and qualitative imaging and cell-biological analysis, to identify and characterize the relevant signal transduction pathways.

Major Research Topics

Molecular mechanisms of division arrest in neural stem cells

Cell proliferation and differentiation in each tissue and organ are controlled strictly in spatial and temporal manner during development. We use Drosophila neural stem cells as a model system to address how cell proliferation coordinates with developmental timing. In Drosophila, all neural cells are produced during the larval and pupal periods, while adult brains have no neural stem cells (Fig.1). We analyze the molecular basis underlying how neural stem cells stop proliferation and undergo differentiation at appropriate developmental timing.

Molecular mechanisms of systemic growth and developmental timing

The final body size in multicellular organisms is determined by two aspects; growth rate and duration of growth phase. In Drosophila, following the embryogenesis, larvae is a specialized stage for nutrient-dependent growth associated with feeding. The final body size is determined by the size at which a larva begins metamorphosis, when the larvae stop feeding. The growth rate and duration in insects are strictly regulated by the endocrine signals such as insulin and steroid hormones (Fig.2). Our research goal is to elucidate the regulatory mechanisms of complex tissue-tissue interactions, which govern nutrient-dependent growth and developmental timing through endocrine signals.

Molecular mechanisms of amino acid signaling

Protein biosynthesis is one critical factor not only for maintaining cell survival but also for limiting cell/tissue growth. The evolutionally conserved TOR protein complex responds to the amino acid signaling and regulates the protein biosyntheses (Fig.3). To clarify the relevant signaling pathway for amino acid sensing, we focus on the molecular mechanisms involved in the activation of the TOR complex by using a combination of biochemical techniques with Drosophila genetics.


  1. Okamoto N. et al., Genes Dev, 27, 87-97, 2013
  2. Okamoto N. et al., PNAS, 109, 2406-2411, 2012
  3. Nishimura T., Tanpakushitsu Kakusan Koso, 9, 1363-1369, 2009
  4. Wirtz-Peitz F. et al., Cell, 5, 161-173, 2008
  5. Nishimura T. et al., Dev Cell, 13, 13-28, 2007
  6. Nishimura T. et al., Mol Biol Cell, 17, 1237-1285, 2006
  7. Nishimura T. et al., Nat Cell Biol, 7, 270-277, 2005
  8. Nishimura T. et al., Nat Cell Biol, 6, 328-334, 2004
  9. Nishimura T. et al., Nat Cell Biol, 5, 819-826, 2003
Fig.1 Larval central nervous system in Drosophila. Neural stem cells (green) and insulin-producing cells (red) are shown.
Fig.2 Drosophila mutants defective for systemic growth. Down regulation of the insulin signaling leads to the formation of small flies. The picture shows brain insulin-producing cell (IPCs) ablated flies and Drosophila insulin receptor (DInR) mutant flies.
Fig.3 Amino acids response in cultured mammalian cell lines. The phosphorylation level of 4EBP1, a downstream target of the TOR kinase, is used as a readout of amino acids (AA) dependent activation of the TOR. Top panels indicate total 4EBP1 levels. Middle panels indicate phosphorylated 4EBP1, while lower panels indicate non-phosphoryated pools of 4EBP1.
Back to Top