Disruption of microtubule integrity initiates mitosis during CNS repair.
Bottom Line: 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).Conversely, loss of Jra renders midline cells unable to replace damaged siblings.The conservation of the identified molecules suggests that similar mechanisms may operate in vertebrates.
Affiliation: School of Biological Sciences, Bangor University, Deiniol Road, Bangor LL57 2UW, UK. firstname.lastname@example.orgShow MeSH
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Mentions: In our pilot study, Miro was the most downregulated transcript (T.B. et al., unpublished data). Miro, encodes a widely conserved atypical GTPase, regulating mitochondrial transport and microtubule stabilization (Guo et al., 2005). If downregulation of Miro permits midline cells to enter into divisions, we would expect more progeny per midline precursor in Miro mutants. Single labeled midline precursors in MiroSD32 mutants do not, however, divide more often than wild-type precursors (data not shown). This is likely due to a maternal contribution of Miro RNA (www.flyexpress.net) and we therefore lowered the amount of Miro RNA by ubiquitously expressing UAS::MiroRNAiTRIPiJF02775 or UAS::MiroRNAiKKi106683 with a maternal GAL4 driver (GAL4V2h). Strikingly, embryos from mothers expressing either of the UAS::MiroRNAi constructs show an increase in midline cell division at the end of germband shortening (Figures 2A, 2B, 2F, and 3C–3F). Compared to control embryos (GAL4V2h) with an average of 4.8 mitotic cells in all 10 trunk neuromeres, the number of midline cell divisions in embryos depleted of Miro increases to an average of 15.6 cells (UAS::MiroRNAiTRIPJF02775) or 11.1 cells (UAS::MiroRNAiKK106683; Figure 2F). If Miro downregulation is essential for damage-induced division, midline targeted upregulation may block these divisions. Indeed, in contrast to wild-type embryos, ablations in early stage 11 embryos with midline Miro expression can result in undamaged cells which survive but neither divide nor differentiate (16%, n = 13; Figure S4). Yet, most ablations result in repair (46%) or death (38%). The low percentage of embryos with no repair may indicate that the expression of Miro in most surviving siblings is not high enough to prevent repair.
Affiliation: School of Biological Sciences, Bangor University, Deiniol Road, Bangor LL57 2UW, UK. email@example.com