title: Disruption of microtubule integrity initiates mitosis during CNS repair.
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.
authors: School of Biological Sciences, Bangor University, Deiniol Road, Bangor LL57 2UW, UK. t.bossing@bangor.ac.uk
authors: Torsten
authors: T
authors: Bossing
authors: Claudia S
authors: CS
authors: Barros
authors: Bettina
authors: B
authors: Fischer
authors: Steven
authors: S
authors: Russell
authors: David
authors: D
authors: Shepherd
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology*; D004789:Enzyme Activation; D008870:Microtubules / Q000737:chemistry / Q000201:enzymology; D008938:Mitosis; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D014404:Tubulin / Q000737:chemistry; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D018808:Transcription Factor AP-1
chemical_list: D029721:Drosophila Proteins; D016755:Proto-Oncogene Proteins c-jun; D014404:Tubulin; D020741:rho GTP-Binding Proteins; C000605629:Jra protein, Drosophila; D018808:Transcription Factor AP-1