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Axotomy-induced HIF-serotonin signalling axis promotes axon regeneration in C. elegans

Author

Listed:
  • Tanimul Alam

    (Graduate School of Science, Nagoya University, Chikusa-ku)

  • Hiroki Maruyama

    (Graduate School of Science, Nagoya University, Chikusa-ku)

  • Chun Li

    (Graduate School of Science, Nagoya University, Chikusa-ku)

  • Strahil Iv. Pastuhov

    (Graduate School of Science, Nagoya University, Chikusa-ku)

  • Paola Nix

    (University of Utah)

  • Michael Bastiani

    (University of Utah)

  • Naoki Hisamoto

    (Graduate School of Science, Nagoya University, Chikusa-ku)

  • Kunihiro Matsumoto

    (Graduate School of Science, Nagoya University, Chikusa-ku)

Abstract

The molecular mechanisms underlying the ability of axons to regenerate after injury remain poorly understood. Here we show that in Caenorhabditis elegans, axotomy induces ectopic expression of serotonin (5-HT) in axotomized non-serotonergic neurons via HIF-1, a hypoxia-inducible transcription factor, and that 5-HT subsequently promotes axon regeneration by autocrine signalling through the SER-7 5-HT receptor. Furthermore, we identify the rhgf-1 and rga-5 genes, encoding homologues of RhoGEF and RhoGAP, respectively, as regulators of axon regeneration. We demonstrate that one pathway initiated by SER-7 acts upstream of the C. elegans RhoA homolog RHO-1 in neuron regeneration, which functions via G12α and RHGF-1. In this pathway, RHO-1 inhibits diacylglycerol kinase, resulting in an increase in diacylglycerol. SER-7 also promotes axon regeneration by activating the cyclic AMP (cAMP) signalling pathway. Thus, HIF-1-mediated activation of 5-HT signalling promotes axon regeneration by activating both the RhoA and cAMP pathways.

Suggested Citation

  • Tanimul Alam & Hiroki Maruyama & Chun Li & Strahil Iv. Pastuhov & Paola Nix & Michael Bastiani & Naoki Hisamoto & Kunihiro Matsumoto, 2016. "Axotomy-induced HIF-serotonin signalling axis promotes axon regeneration in C. elegans," Nature Communications, Nature, vol. 7(1), pages 1-11, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10388
    DOI: 10.1038/ncomms10388
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