Trombley, S., Powell, J., Guttipatti, P., Matamoros, A., Lin, X., O'Harrow, T., Steinschaden, T., Miles, L., Wang, Q., Wang, S., Qiu, J., Li, Q., Li, F., Song, Y. (2023). Glia instruct axon regeneration via a ternary modulation of neuronal calcium channels in Drosophila.  Nat. Commun. 14(1): 6490.

FBrf0257812

Research paper

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 Ca[2+] 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 Ca[2+] transients. Together, we identify a multifaceted glia-neuron coupling which can be hijacked to promote neural repair.

PMC10576831 (PMC) (EuropePMC)