Disruption of microtubule integrity initiates mitosis during CNS repair
Torsten Bossing1, Claudia S Barros, Bettina Fischer
1School of Biological Sciences, Bangor University, Deiniol Road, Bangor LL57 2UW, UK. t.bossing@bangor.ac.uk
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.
Insights
Traumatic brain injury in fruit flies triggers cell division for CNS repair. Microtubule integrity and specific proteins like Miro and Jra are key to this regenerative process, suggesting conserved mechanisms in vertebrates.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- Mechanisms of central nervous system (CNS) repair are crucial for treating neurological injuries.
- Understanding cellular responses to CNS damage is vital for developing therapeutic strategies.
Purpose of the Study:
- To investigate the cellular and molecular mechanisms underlying CNS repair after traumatic injury in Drosophila.
- To identify key regulators of cell division during CNS regeneration.
Main Methods:
- Analysis of single-cell transcriptomes during CNS repair in Drosophila.
- Manipulation of gene expression (Miro, Jra) and microtubule dynamics.
- Assessment of cell division and cytoskeletal integrity in response to injury.
Main Results:
- Traumatic injury to the embryonic Drosophila CNS activates cell division for repair.
- Downregulation of mitochondrial Rho (Miro) and upregulation of Jun-related antigen (Jra) are observed during repair.
- Microtubule cytoskeleton integrity is a critical regulator of cell division and Jra expression post-injury.
- Miro regulates microtubule stability and cell division, while Jra is essential for replacing lost cells.
Conclusions:
- The microtubule cytoskeleton plays a pivotal role in controlling cell division during CNS midline repair following injury.
- The identified molecular players (Miro, Jra) and mechanisms are conserved, suggesting potential relevance to vertebrate CNS repair.
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