A novel Drosophila injury model reveals severed axons are cleared through a draper/MMP-1 signaling cascade

Maria D. Purice, Arpita Ray, Eva Jolanda Münzel, Bernard J. Pope, Daniel J. Park, Sean Speese, Mary Logan

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere23611
JournaleLife
Volume6
DOIs
StatePublished - Aug 21 2017

Fingerprint

Matrix Metalloproteinase 1
Neuroglia
Drosophila
Axons
Wounds and Injuries
RNA Sequence Analysis
Axotomy
Neuropil
Transcription Factor AP-1
Innate Immunity
Debris
Gene expression
Diptera
Neurons
Assays
Genes
Chemical activation
RNA
Gene Expression

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

A novel Drosophila injury model reveals severed axons are cleared through a draper/MMP-1 signaling cascade. / Purice, Maria D.; Ray, Arpita; Münzel, Eva Jolanda; Pope, Bernard J.; Park, Daniel J.; Speese, Sean; Logan, Mary.

In: eLife, Vol. 6, e23611, 21.08.2017.

Research output: Contribution to journalArticle

Purice, Maria D. ; Ray, Arpita ; Münzel, Eva Jolanda ; Pope, Bernard J. ; Park, Daniel J. ; Speese, Sean ; Logan, Mary. / A novel Drosophila injury model reveals severed axons are cleared through a draper/MMP-1 signaling cascade. In: eLife. 2017 ; Vol. 6.
@article{c1331535964a4d20a58e66dfe707ce9f,
title = "A novel Drosophila injury model reveals severed axons are cleared through a draper/MMP-1 signaling cascade",
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.",
author = "Purice, {Maria D.} and Arpita Ray and M{\"u}nzel, {Eva Jolanda} and Pope, {Bernard J.} and Park, {Daniel J.} and Sean Speese and Mary Logan",
year = "2017",
month = "8",
day = "21",
doi = "10.7554/eLife.23611",
language = "English (US)",
volume = "6",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",

}

TY - JOUR

T1 - A novel Drosophila injury model reveals severed axons are cleared through a draper/MMP-1 signaling cascade

AU - Purice, Maria D.

AU - Ray, Arpita

AU - Münzel, Eva Jolanda

AU - Pope, Bernard J.

AU - Park, Daniel J.

AU - Speese, Sean

AU - Logan, Mary

PY - 2017/8/21

Y1 - 2017/8/21

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85029219432&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85029219432&partnerID=8YFLogxK

U2 - 10.7554/eLife.23611

DO - 10.7554/eLife.23611

M3 - Article

C2 - 28825401

AN - SCOPUS:85029219432

VL - 6

JO - eLife

JF - eLife

SN - 2050-084X

M1 - e23611

ER -