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Glia instruct axon regeneration via a ternary modulation of neuronal calcium channels in Drosophila

Author

Listed:
  • Shannon Trombley

    (The Children’s Hospital of Philadelphia)

  • Jackson Powell

    (The Children’s Hospital of Philadelphia)

  • Pavithran Guttipatti

    (The Children’s Hospital of Philadelphia)

  • Andrew Matamoros

    (The Children’s Hospital of Philadelphia
    University of Pennsylvania)

  • Xiaohui Lin

    (Fudan University)

  • Tristan O’Harrow

    (The Children’s Hospital of Philadelphia)

  • Tobias Steinschaden

    (The Children’s Hospital of Philadelphia)

  • Leann Miles

    (The Children’s Hospital of Philadelphia)

  • Qin Wang

    (The Children’s Hospital of Philadelphia
    University of Pennsylvania)

  • Shuchao Wang

    (The Children’s Hospital of Philadelphia)

  • Jingyun Qiu

    (The Children’s Hospital of Philadelphia)

  • Qingyang Li

    (Fudan University)

  • Feng Li

    (Fudan University)

  • Yuanquan Song

    (The Children’s Hospital of Philadelphia
    University of Pennsylvania)

Abstract

A neuron’s regenerative capacity is governed by its intrinsic and extrinsic environment. Both peripheral and central neurons exhibit cell-type-dependent axon regeneration, but the underlying mechanism is unclear. Glia provide a milieu essential for regeneration. However, the routes of glia-neuron signaling remain underexplored. Here, we show that regeneration specificity is determined by the axotomy-induced Ca2+ transients only in the fly regenerative neurons, which is mediated by L-type calcium channels, constituting the core intrinsic machinery. Peripheral glia regulate axon regeneration via a three-layered and balanced modulation. Glia-derived tumor necrosis factor acts through its neuronal receptor to maintain calcium channel expression after injury. Glia sustain calcium channel opening by enhancing membrane hyperpolarization via the inwardly-rectifying potassium channel (Irk1). Glia also release adenosine which signals through neuronal adenosine receptor (AdoR) to activate HCN channels (Ih) and dampen Ca2+ transients. Together, we identify a multifaceted glia-neuron coupling which can be hijacked to promote neural repair.

Suggested Citation

  • Shannon Trombley & Jackson Powell & Pavithran Guttipatti & Andrew Matamoros & Xiaohui Lin & Tristan O’Harrow & Tobias Steinschaden & Leann Miles & Qin Wang & Shuchao Wang & Jingyun Qiu & Qingyang Li &, 2023. "Glia instruct axon regeneration via a ternary modulation of neuronal calcium channels in Drosophila," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42306-2
    DOI: 10.1038/s41467-023-42306-2
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