The glial regenerative response to central nervous system injury is enabled by pros-notch and pros-NFκB feedback.
Organisms are structurally robust, as cells accommodate changes preserving structural integrity and function. The molecular mechanisms underlying structural robustness and plasticity are poorly understood, but can be investigated by probing how cells respond to injury. Injury to the CNS induces prol...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-08-01
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| Series: | PLoS Biology |
| Online Access: | https://doi.org/10.1371/journal.pbio.1001133 |
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| author | Kentaro Kato Manuel G Forero Janine C Fenton Alicia Hidalgo |
| author_facet | Kentaro Kato Manuel G Forero Janine C Fenton Alicia Hidalgo |
| author_sort | Kentaro Kato |
| collection | DOAJ |
| description | Organisms are structurally robust, as cells accommodate changes preserving structural integrity and function. The molecular mechanisms underlying structural robustness and plasticity are poorly understood, but can be investigated by probing how cells respond to injury. Injury to the CNS induces proliferation of enwrapping glia, leading to axonal re-enwrapment and partial functional recovery. This glial regenerative response is found across species, and may reflect a common underlying genetic mechanism. Here, we show that injury to the Drosophila larval CNS induces glial proliferation, and we uncover a gene network controlling this response. It consists of the mutual maintenance between the cell cycle inhibitor Prospero (Pros) and the cell cycle activators Notch and NFκB. Together they maintain glia in the brink of dividing, they enable glial proliferation following injury, and subsequently they exert negative feedback on cell division restoring cell cycle arrest. Pros also promotes glial differentiation, resolving vacuolization, enabling debris clearance and axonal enwrapment. Disruption of this gene network prevents repair and induces tumourigenesis. Using wound area measurements across genotypes and time-lapse recordings we show that when glial proliferation and glial differentiation are abolished, both the size of the glial wound and neuropile vacuolization increase. When glial proliferation and differentiation are enabled, glial wound size decreases and injury-induced apoptosis and vacuolization are prevented. The uncovered gene network promotes regeneration of the glial lesion and neuropile repair. In the unharmed animal, it is most likely a homeostatic mechanism for structural robustness. This gene network may be of relevance to mammalian glia to promote repair upon CNS injury or disease. |
| format | Article |
| id | doaj-art-64016a298a9d423bb2f07aca4fb65480 |
| institution | OA Journals |
| issn | 1544-9173 1545-7885 |
| language | English |
| publishDate | 2011-08-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj-art-64016a298a9d423bb2f07aca4fb654802025-08-20T02:34:06ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852011-08-0198e100113310.1371/journal.pbio.1001133The glial regenerative response to central nervous system injury is enabled by pros-notch and pros-NFκB feedback.Kentaro KatoManuel G ForeroJanine C FentonAlicia HidalgoOrganisms are structurally robust, as cells accommodate changes preserving structural integrity and function. The molecular mechanisms underlying structural robustness and plasticity are poorly understood, but can be investigated by probing how cells respond to injury. Injury to the CNS induces proliferation of enwrapping glia, leading to axonal re-enwrapment and partial functional recovery. This glial regenerative response is found across species, and may reflect a common underlying genetic mechanism. Here, we show that injury to the Drosophila larval CNS induces glial proliferation, and we uncover a gene network controlling this response. It consists of the mutual maintenance between the cell cycle inhibitor Prospero (Pros) and the cell cycle activators Notch and NFκB. Together they maintain glia in the brink of dividing, they enable glial proliferation following injury, and subsequently they exert negative feedback on cell division restoring cell cycle arrest. Pros also promotes glial differentiation, resolving vacuolization, enabling debris clearance and axonal enwrapment. Disruption of this gene network prevents repair and induces tumourigenesis. Using wound area measurements across genotypes and time-lapse recordings we show that when glial proliferation and glial differentiation are abolished, both the size of the glial wound and neuropile vacuolization increase. When glial proliferation and differentiation are enabled, glial wound size decreases and injury-induced apoptosis and vacuolization are prevented. The uncovered gene network promotes regeneration of the glial lesion and neuropile repair. In the unharmed animal, it is most likely a homeostatic mechanism for structural robustness. This gene network may be of relevance to mammalian glia to promote repair upon CNS injury or disease.https://doi.org/10.1371/journal.pbio.1001133 |
| spellingShingle | Kentaro Kato Manuel G Forero Janine C Fenton Alicia Hidalgo The glial regenerative response to central nervous system injury is enabled by pros-notch and pros-NFκB feedback. PLoS Biology |
| title | The glial regenerative response to central nervous system injury is enabled by pros-notch and pros-NFκB feedback. |
| title_full | The glial regenerative response to central nervous system injury is enabled by pros-notch and pros-NFκB feedback. |
| title_fullStr | The glial regenerative response to central nervous system injury is enabled by pros-notch and pros-NFκB feedback. |
| title_full_unstemmed | The glial regenerative response to central nervous system injury is enabled by pros-notch and pros-NFκB feedback. |
| title_short | The glial regenerative response to central nervous system injury is enabled by pros-notch and pros-NFκB feedback. |
| title_sort | glial regenerative response to central nervous system injury is enabled by pros notch and pros nfκb feedback |
| url | https://doi.org/10.1371/journal.pbio.1001133 |
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