Journal
ELIFE
Volume 6, Issue -, Pages -Publisher
ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.23611
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Funding
- Glenn Foundation for Medical Research Glenn/AFAR Scholarship for Research in the Biology of Aging
- National Institutes of Health NIH Neuroscience of Aging Training Grant [T32AG023477]
- National Institute of Neurological Disorders and Stroke [R21 NS084112, R01 NS079387-01]
- Fred W. Fields Foundation New Investigator Award
- Medical Research Foundation of Oregon New Investigator Grant
- Ken and Ginger Harrison Term Professor Award Faculty Award
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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.
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