Abstract
Neural injury triggers swift responses from glia, including glial migration and phagocytic clearance of damaged neurons. The transcriptional programs governing these complex innate glial immune responses are still unclear. Here, we describe a novel injury assay in adult Drosophila that elicits widespread glial responses in the ventral nerve cord (VNC). We profiled injury-induced changes in VNC gene expression by RNA sequencing (RNA-seq) and found that responsive genes fall into diverse signaling classes. One factor, matrix metalloproteinase-1 (MMP-1), is induced in Drosophila ensheathing glia responding to severed axons. Interestingly, glial induction of MMP-1 requires the highly conserved engulfment receptor Draper, as well as AP-1 and STAT92E. In MMP-1 depleted flies, glia do not properly infiltrate neuropil regions after axotomy and, as a consequence, fail to clear degenerating axonal debris. This work identifies Draper-dependent activation of MMP-1 as a novel cascade required for proper glial clearance of severed axons.
Highlights
Glial cells exhibit swift and dramatic responses to any form of neural trauma
We turned to the ventral nerve cord (VNC) of the fly with the goal of establishing a more robust in vivo nerve injury assay to query changes in glial gene expression
We assessed STAT92E activity in the VNC by using the in vivo reporter 10XSTAT92E-dGFP, which contains 10 tandem STAT92E binding sites upstream of destabilized GFP (Bach et al, 2007). dGFP was undetectable in uninjured VNCs, but following ablation of front legs and wings, we observed a striking increase in dGFP expression only in the corresponding neuropil regions and surrounding cortex (Figure 3b). These results indicate that AP-1 and STAT92E are activated in VNC glia after axotomy and suggest that common transcriptional programs are stimulated throughout the adult nervous system in response to nerve injury
Summary
Glial cells exhibit swift and dramatic responses to any form of neural trauma These reactions provide neuroprotection and minimize further damage to the central nervous system Glial activation of the c-Jun N-terminal kinase (JNK) pathway and the downstream transcriptional heterodimer AP-1, which consists of c-Fos and c-Jun, has been reported in various injury and disease models (Anderson et al, 1994; Pennypacker et al, 1994; Yu et al, 1995). It remains unclear what pathways are required to initiate these transcriptional programs and how they drive complex glial responses to neural injury
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