Laboratory for Neuronal Growth Mechanisms

The development of functional neuronal networks relies on the spatial accuracy of axon extension. Each extending axon is tipped by a growth cone that can interpret extracellular "guidance cues" and navigate the axon along the correct path. After neuronal networks have been developed, injury to the adult central nervous system induces the formation of barriers to regenerating axons. It is well known that growth cones use similar mechanisms for their navigation during development and regeneration. Our aim is to investigate growth cone navigation with particular emphasis on the roles of guidance cues, intracellular signals, cytoskeleton, adhesion machinery and membrane dynamics. These revelations will help elucidate the fundamental principles of axon tract formation and establish the molecular and cellular biological basis for axon tract repair.

Research Subjects

• Intracellular signals that regulate axon growth and guidance
• Cytoskeletal and membrane dynamics for growth cone navigation
• Lipids and sugars that control neuronal network formation

Publications

1. Tojima, T., Hines, J.H., Henley, J.R., and Kamiguchi, H.:
   "Second messengers and membrane trafficking direct and organize growth cone steering"
   Nature Reviews Neuroscience 12, 191-203 (2011)
2. Akiyama, H. and Kamiguchi, H.:
   "Phosphatidylinositol 3-kinase facilitates microtubule-dependent membrane transport for neuronal growth cone guidance."
   The Journal of Biological Chemistry 285, 41740-41748 (2010)
3. Tojima, T., Itofusa, R., and Kamiguchi, H.:
   "Asymmetric clathrin-mediated endocytosis drives repulsive growth cone guidance."
   Neuron 66, 370-377 (2010)
4. Tamada, A., Kawase, S., Murakami, F., and Kamiguchi, H.:
   "Autonomous right-screw rotation of growth cone filopodia drives neurite turning."
   The Journal of Cell Biology 188, 429-441(2010)
5. Akiyama, H., Matsu-ura, T., Mikoshiba, K., and Kamiguchi, H.:
   "Control of neuronal growth cone navigation by asymmetric inositol 1,4,5-trisphosphate signals."
   Science Signaling 2, ra34 (2009)
6. Tojima, T., Itofusa, R., and Kamiguchi, H.:
   "The nitric oxide-cyclic GMP pathway controls the directional polarity of growth cone guidance via modulating cytosolic Ca2+ signals."
   The Journal of Neuroscience 29, 7886-7897 (2009)
7. Tojima, T., Akiyama, H., Itofusa, R., Li, Y., Katayama, H., Miyawaki, A., and Kamiguchi, H.:
   "Attractive axon guidance involves asymmetric membrane transport and exocytosis in the growth cone."
   Nature Neuroscience 10, 58-66 (2007)
8. Ooashi, N., Futatsugi, A., Yoshihara, F., Mikoshiba, K., and Kamiguchi, H.:
   "Cell adhesion molecules regulate Ca2+-mediated steering of growth cones via cyclic AMP and ryanodine receptor type3."
   The Journal of Cell Biology 170, 1159-1167 (2005)
9. Nishimura, K., Yoshihara, F., Tojima, T., Ooashi, N., Yoon, W., Mikoshiba, K., Bennett, V., and Kamiguchi, H.:
   "L1-dependent neuritogenesis involves ankyrinB that mediates L1-CAM coupling with retrograde actin flow."
   The Journal of Cell Biology 163, 1077-1088 (2003)
10. Nakai, Y. and Kamiguchi, H.:
    "Migration of nerve growth cones requires detergent-resistant membranes in a spatially defined and substrate-dependent manner."
    The Journal of Cell Biology 159, 1097-1108 (2002)