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. email@example.comShow MeSH
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Mentions: Jun is a transcription factor found to be upregulated in vertebrate brain injury (Raivich and Behrens, 2006). Interestingly we observed upregulation of the Drosophila Jun ortholog, Jra, in our exploratory microarray analysis (T.B. et al., unpublished data). To test if Jra is necessary for damage-induced division, we first performed mass ablation of midline cells in JraIA109 mutants. In heterozygous embryos, tissue repair is still observed (4/9; Figure 4A) but in Jra homozygous mutants injury no longer activates midline cell division (0/5; Figure 4B). Without damage, we detect no significant changes in midline cell divisions between heterozygous and homozygous Jra mutant embryos (Figures S4D–S4F). We next ablated single cells in heterozygous and homozygous Jra mutant embryos. In heterozygous embryos, single ablated sibling cells were mostly replaced (62%, n = 21; Figures 4C and 4E); however, in Jra homozygotes the replacement of ablated single cells is the exception (14%). The majority of surviving siblings do not divide or differentiate (57%, n = 14; Figures 4D and 4E). Since midline expression of α-tubulin drives midline cells into division, we tested if α-tubulin expression is sufficient to switch on Jra transcription. Indeed, midline targeted α-tubulin induces ectopic Jra expression (Figures 4F and 4G).
Affiliation: School of Biological Sciences, Bangor University, Deiniol Road, Bangor LL57 2UW, UK. firstname.lastname@example.org