Faculty Detail / 研究室詳細

Hiroyuki Kamiguchi, M.D., Ph.D.

- Understanding molecular mechanisms that control neuronal circuit formation and regeneration.

Neuronal Growth Mechanisms

Senior Team Leader

Axon guidance, Growth cone, Signal transduction

Hiroyuki  Kamiguchi

Research Area

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.

Extracellular gradients of guidance cues trigger the generation of cytosolic Ca2+ signals on one side of growth cones (orange areas). The growth cone turning direction depends on the source of Ca2+. These Ca2+ signals mediate bidirectional turning through asymmetric membrane trafficking, with exocytosis driving attraction and endocytosis driving repulsion.

Selected Publications View All

  1. 1

    Guy AT, Nagatsuka Y, Ooashi N, Inoue M, Nakata A, Greimel P, Inoue A, Nabetani T, Murayama A, Ohta K, Ito Y, Aoki J, Hirabayashi Y, and Kamiguchi H: "Glycerophospholipid regulation of modality-specific sensory axon guidance in the spinal cord.", Science, 349(6251), 974-977 (2015)

  2. 2

    Tojima T, Itofusa R, and Kamiguchi H: "Steering Neuronal Growth Cones by Shifting the Imbalance between Exocytosis and Endocytosis.", J Neurosci, 34(21), 7165-78 (2014)

  3. 3

    Tojima T, Hines JH, Henley JR, and Kamiguchi H: "Second messengers and membrane trafficking direct and organize growth cone steering.", Nat Rev Neurosci, 12(4), 191-203 (2011)

  4. 4

    Akiyama H, and Kamiguchi H: "Phosphatidylinositol 3-kinase facilitates microtubule-dependent membrane transport for neuronal growth cone guidance.", J Biol Chem, 285(53), 41740-8 (2010)

  5. 5

    Tojima T, Itofusa R, and Kamiguchi H: "Asymmetric clathrin-mediated endocytosis drives repulsive growth cone guidance.", Neuron, 66(3), 370-7 (2010)

  6. 6

    Tamada A, Kawase S, Murakami F, and Kamiguchi H: "Autonomous right-screw rotation of growth cone filopodia drives neurite turning.", J Cell Biol, 188(3), 429-41 (2010)

  7. 7

    Akiyama H, Matsu-ura T, Mikoshiba K, and Kamiguchi H: "Control of neuronal growth cone navigation by asymmetric inositol 1,4,5-trisphosphate signals.", Sci Signal, 2(79), ra34 (2009)

  8. 8

    Tojima T, Itofusa R, and Kamiguchi H: "The nitric oxide-cGMP pathway controls the directional polarity of growth cone guidance via modulating cytosolic Ca2+ signals.", J Neurosci, 29(24), 7886-97 (2009)

  9. 9

    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.", Nat Neurosci, 10(1), 58-66 (2007)

  10. 10

    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 type 3.", J Cell Biol, 170(7), 1159-67 (2005)

Press Releases View All