Academic Appointments

  • Basic Life Science Research Associate, Biology

All Publications

  • Two Wnts Instruct Topographic Synaptic Innervation in C-elegans CELL REPORTS Mizumoto, K., Shen, K. 2013; 5 (2): 389-396


    Gradients of topographic cues play essential roles in the organization of sensory systems by guiding axonal growth cones. Little is known about whether there are additional mechanisms for precise topographic mapping of synaptic connections. Whereas the C. elegans DA8 and DA9 neurons have similar axonal trajectories, their synapses are positioned in distinct but adjacent domains in the anterior-posterior axis. We found that two Wnts, LIN-44 and EGL-20, are responsible for this spatial organization of synapses. Both Wnts form putative posterior-high, anterior-low gradients. The posteriorly expressed LIN-44 inhibits synapse formation in both DA9 and DA8, and creates a synapse-free domain on both axons via LIN-17 /Frizzled. EGL-20, a more anteriorly expressed Wnt, inhibits synapse formation through MIG-1/Frizzled, which is expressed in DA8 but not in DA9. The Wnt-Frizzled specificity and selective Frizzled expression dictate the stereotyped, topographic positioning of synapses between these two neurons.

    View details for DOI 10.1016/j.celrep.2013.09.011

    View details for Web of Science ID 000328263000012

    View details for PubMedID 24139806

  • Interaxonal Interaction Defines Tiled Presynaptic Innervation in C. elegans NEURON Mizumoto, K., Shen, K. 2013; 77 (4): 655-666


    Cellular interactions between neighboring axons are essential for global topographic map formation. Here we show that axonal interactions also precisely instruct the location of synapses. Motoneurons form en passant synapses in Caenorhabditis elegans. Although axons from the same neuron class significantly overlap, each neuron innervatesĀ a unique and tiled segment of the muscle field by restricting its synapses to a distinct subaxonal domain-a phenomenon we term synaptic tiling. Using DA8 and DA9 motoneurons, we found that the synaptic tiling requires the PlexinA4 homolog, PLX-1, and two transmembrane semaphorins. In the plexin or semaphorin mutants, synaptic domains from both neurons expand and overlap with each other without guidance defects. In a semaphorin-dependent manner, PLX-1 is concentrated at the synapse-free axonal segment, delineating the tiling border. Furthermore, plexin inhibits presynapse formation by suppressing synaptic F-actin through its cytoplasmic GTPase-activating protein (GAP) domain. Hence, contact-dependent, intra-axonal plexin signaling specifies synaptic circuits by inhibiting synapse formation at the subcellular loci. VIDEO ABSTRACT:

    View details for DOI 10.1016/j.neuron.2012.12.031

    View details for Web of Science ID 000315561300009

    View details for PubMedID 23439119