Laboratory for Morphogenetic Signaling

The goal of this laboratory is to understand how cellular activities such as cell motility and adhesion are coordinated to build higher-order structures of tissue, organ and organisms. To tackle this problem, we mainly use the model organism Drosophila that is suited for genetic dissection of biological processes and for high-resolution imaging. We address the problem at three levels of cellular organization: single cell, multiple cells, and organ. In the study of multicellular level, we addressed the question of how epithelial cell sheets are remodeled to build higher-order structures of the tracheal system, which forms a stereotyped network of epithelial tubules. We have extensively studied details of cell shape and cell interaction control during invagination of tracheal placode, the first step of three-dimensional morphogenesis. We have also elucidated the mechanism of target recognition and adhesion of tracheal branch connection, and subsequent fusion of tubules. In the single cell level approach, we study cell elongation in order to reveal essential roles of cytoskeletons in cell shape morphogenesis. We have chosen two model cells, bristles and spermatids, each representing extreme example of robust cell elongation and are suitable for application of high-resolution imaging techniques. In the case of bristle elongation, we have unveiled the novel role of polarized trafficking of recycling endosome and its upstream regulator IKK epsilon in sustaining robust cell elongation processes. In the case of spermatid elongation, a feed forward mechanism involving mutual activation of cytoplasmic microtubules and mitochondria was found to be essential for maintaining active growth zone at the tip of sperm tail. Finally we attempted to apply cell biological information to understand the process of higher-order structure of the insect and other protostome limbs in the context to evolution.

Research Subjects

• Dynamics of epithelial architectures in morphogenesis
• Control of cytoskeletons in cell morphogenesis
• Mechanisms of insect limb development

Publications

1. Kondo T., Hayashi S.:
   "Mitotic cell rounding accelerates epithelial invagination"
   Nature 494(7435): 125-129(2013)
2. Dong B, Kakihara K, Otani T, Wada H, Hayashi S.:
   "Rab9 and retromer regulate retrograde trafficking of luminal protein required for epithelial tube length control."
   Nature Communications 4: 1358(2013)
3. Otani, T., Oshima,K., Onishi, S., Takeda,M., Yonemura, S.,and Hayashi, S.:
   "IKKε regulates cell elongation through recycling endosome shuttling"
   Developmental Cell 20: 1-14(2011)
4. Tajiri R, Misaki K, Yonemura S, Hayashi S.:
   "Joint morphology in the insect leg: evolutionary history inferred from Notch loss-of-function phenotypes in Drosophila."
   Development 138(21):4621-6(2011)
5. Noguchi, T., Koizumi,M., and Hayashi, S.:
   "Sustained elongation of sperm tail promoted by local remodeling of giant mitochondria in Drosophila."
   Current Biology 21(10):805-14(2011)
6. Tajiri, R., Misaki, K., Yonemura, S., and Hayashi, S.:
   "Dynamic shape changes of ECM-producing cells drive morphogenesis of ball-and-socket joints in the fly leg"
   Development 137: 2055-2063(2010)
7. Kawahashi, K., and Hayashi, S.:
   "Dynamic intracellular distribution of Notch during activation and asymmetric cell division revealed by functional fluorescent fusion proteins"
   Genes to Cells 15 :749-759(2010)
8. Niwa, N., Akimoto-Kato, A., Niimi, T., Tojo, K., Machida, R., and Hayashi, S.:
   "Evolutionary origin of the insect wing via integration of two developmental modules"
   Evolution & Development 12: 168-176(2010)
9. Kaido,M., Wada,H., Shindo,M., and Hayashi,S.:
   "Essential requirement for RING finger E3 ubiquitin ligase Hakai in early embryonic development of Drosophila"
   Genes to Cells 14:1067-1077(2009)
10. Kakihara,K., Shinmyozu,K., Kato,K., Wada,H., Hayashi,S.:
    "Conversion of plasma membrane topology during epithelial tube connection requires Arf-like 3 small GTPase in Drosophila"
    Mechanisms of Development , 125(3-4):325-336 (2008)