Disruption of microtubule integrity initiates mitosis during CNS repair
Disruption of microtubule integrity initiates mitosis during CNS repair
Mechanisms of CNS repair have vital medical implications. We show that traumatic injury to the ventral midline of the embryonic Drosophila CNS activates cell divisions to replace lost cells. A pilot screen analyzing transcriptomes of single cells during repair pointed to downregulation of the microtubule-stabilizing GTPase mitochondrial Rho (Miro) and upregulation of the Jun transcription factor Jun-related antigen (Jra). Ectopic Miro expression can prevent midline divisions after damage, whereas Miro depletion destabilizes cortical β-tubulin and increases divisions. Disruption of cortical microtubules, either by chemical depolymerization or by overexpression of monomeric tubulin, triggers ectopic mitosis in the midline and induces Jra expression. Conversely, loss of Jra renders midline cells unable to replace damaged siblings. Our data indicate that upon injury, the integrity of the microtubule cytoskeleton controls cell division in the CNS midline, triggering extra mitosis to replace lost cells. The conservation of the identified molecules suggests that similar mechanisms may operate in vertebrates.
Animals, Cell Differentiation, Drosophila Proteins/metabolism, Drosophila melanogaster/cytology, Enzyme Activation, Microtubules/chemistry, Mitosis, Proto-Oncogene Proteins c-jun/metabolism, Tubulin/chemistry, rho GTP-Binding Proteins/metabolism
433-40
Bossing, Torsten
f409f6b8-1be9-44d1-bbc2-0d3437967f66
Barros, Claudia S
1d07ab31-2723-4298-8b46-690b67d10284
Fischer, Bettina
c142a2f6-a8f2-4afa-a98d-3d7193b2a9c4
Russell, Steven
b50e1f38-ab5a-4049-95f1-03a1593fc0ae
Shepherd, David
11aa6858-d19c-4450-82ff-11dff9dcd9c4
14 August 2012
Bossing, Torsten
f409f6b8-1be9-44d1-bbc2-0d3437967f66
Barros, Claudia S
1d07ab31-2723-4298-8b46-690b67d10284
Fischer, Bettina
c142a2f6-a8f2-4afa-a98d-3d7193b2a9c4
Russell, Steven
b50e1f38-ab5a-4049-95f1-03a1593fc0ae
Shepherd, David
11aa6858-d19c-4450-82ff-11dff9dcd9c4
Bossing, Torsten, Barros, Claudia S, Fischer, Bettina, Russell, Steven and Shepherd, David
(2012)
Disruption of microtubule integrity initiates mitosis during CNS repair.
Developmental Cell, 23 (2), .
(doi:10.1016/j.devcel.2012.06.002).
Abstract
Mechanisms of CNS repair have vital medical implications. We show that traumatic injury to the ventral midline of the embryonic Drosophila CNS activates cell divisions to replace lost cells. A pilot screen analyzing transcriptomes of single cells during repair pointed to downregulation of the microtubule-stabilizing GTPase mitochondrial Rho (Miro) and upregulation of the Jun transcription factor Jun-related antigen (Jra). Ectopic Miro expression can prevent midline divisions after damage, whereas Miro depletion destabilizes cortical β-tubulin and increases divisions. Disruption of cortical microtubules, either by chemical depolymerization or by overexpression of monomeric tubulin, triggers ectopic mitosis in the midline and induces Jra expression. Conversely, loss of Jra renders midline cells unable to replace damaged siblings. Our data indicate that upon injury, the integrity of the microtubule cytoskeleton controls cell division in the CNS midline, triggering extra mitosis to replace lost cells. The conservation of the identified molecules suggests that similar mechanisms may operate in vertebrates.
Text
1-s2.0-S1534580712002754-main
- Version of Record
More information
Published date: 14 August 2012
Keywords:
Animals, Cell Differentiation, Drosophila Proteins/metabolism, Drosophila melanogaster/cytology, Enzyme Activation, Microtubules/chemistry, Mitosis, Proto-Oncogene Proteins c-jun/metabolism, Tubulin/chemistry, rho GTP-Binding Proteins/metabolism
Identifiers
Local EPrints ID: 455320
URI: http://eprints.soton.ac.uk/id/eprint/455320
ISSN: 1534-5807
PURE UUID: 19fb9eb4-db32-4376-a64a-79ce8666b86f
Catalogue record
Date deposited: 16 Mar 2022 18:08
Last modified: 16 Mar 2024 16:15
Export record
Altmetrics
Contributors
Author:
Torsten Bossing
Author:
Claudia S Barros
Author:
Bettina Fischer
Author:
Steven Russell
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics