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bioRxiv · 10.1101/2025.07.21.665563

Nerve injury promotes glial immune responses through a Draper/Ninjurin A pathway

Brashaw, C.·Griffin, A.·Speese, S. D.·Logan, M. A.
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Abstract

Degenerating neurons elicit striking immune reactions from glial cells, including directed invasion of injury sites and engulfment of neuronal debris. While these conserved glial immune responses are neuroprotective, our mechanistic understanding of glial immunity in the damaged and diseased brain is still incomplete. Here, using an in vivo nerve injury assay in the adult Drosophila olfactory system, we characterize a novel role for the transmembrane adhesion molecule Ninjurin A (NijA). We show that NijA is transcriptionally upregulated in neuropil ensheathing glia, but not local astrocytes, within hours after olfactory nerve transection. In NijA mutants, glia fail to properly infiltrate areas that contain severed olfactory nerves, and degenerating axonal debris is not cleared from the CNS. One well-defined signaling cascade critical for ensheathing glial clearance of damaged olfactory axons is the conserved MEGF10/Draper pathway, which includes the engulfment receptor Draper, downstream transcriptional complex AP-1, and known gene target MMP-1. We show that injury-induced transcription of NijA in responding glia requires the Draper receptor but is independent of MMP-1, suggesting a parallel signaling cascade is activated downstream of Draper in responding glia. Our findings reveal an essential role for the glial adhesion factor NijA in morphological and phagocytic responses to CNS damage, highlighting this conserved molecule as a new potential glial therapeutic target for neurodegenerative conditions.

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Brashaw, C., Griffin, A., Speese, S. D., Logan, M. A.. 2025-07-25. Nerve injury promotes glial immune responses through a Draper/Ninjurin A pathway. https://doi.org/10.1101/2025.07.21.665563

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