The regeneration-responsive element careg monitors activation of Müller glia after MNU-induced damage of photoreceptors in the zebrafish retina.

Autor:	Bise T; Department of Biology, University of Fribourg, Fribourg, Switzerland., Pfefferli C; Department of Biology, University of Fribourg, Fribourg, Switzerland., Bonvin M; Department of Biology, University of Fribourg, Fribourg, Switzerland., Taylor L; Interfaculty Bioinformatics Unit, University of Bern, Bern, Switzerland.; Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland., Lischer HEL; Interfaculty Bioinformatics Unit, University of Bern, Bern, Switzerland.; Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland., Bruggmann R; Interfaculty Bioinformatics Unit, University of Bern, Bern, Switzerland.; Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland., Jaźwińska A; Department of Biology, University of Fribourg, Fribourg, Switzerland.
Jazyk:	angličtina
Zdroj:	Frontiers in molecular neuroscience [Front Mol Neurosci] 2023 Apr 17; Vol. 16, pp. 1160707. Date of Electronic Publication: 2023 Apr 17 (Print Publication: 2023).
DOI:	10.3389/fnmol.2023.1160707
Abstrakt:	In contrast to mammals, zebrafish can regenerate their damaged photoreceptors. This capacity depends on the intrinsic plasticity of Müller glia (MG). Here, we identified that the transgenic reporter careg , a marker of regenerating fin and heart, also participates in retina restoration in zebrafish. After methylnitrosourea (MNU) treatment, the retina became deteriorated and contained damaged cell types including rods, UV-sensitive cones and the outer plexiform layer. This phenotype was associated with the induction of careg expression in a subset of MG until the reconstruction of the photoreceptor synaptic layer. Single-cell RNA sequencing (scRNAseq) analysis of regenerating retinas revealed a population of immature rods, defined by high expression of rhodopsin and the ciliogenesis gene meig1 , but low expression of phototransduction genes. Furthermore, cones displayed deregulation of metabolic and visual perception genes in response to retina injury. Comparison between careg:EGFP expressing and non-expressing MG demonstrated that these two subpopulations are characterized by distinct molecular signatures, suggesting their heterogenous responsiveness to the regenerative program. Dynamics of ribosomal protein S6 phosphorylation showed that TOR signaling became progressively switched from MG to progenitors. Inhibition of TOR with rapamycin reduced the cell cycle activity, but neither affected careg:EGFP expression in MG, nor prevented restoration of the retina structure. This indicates that MG reprogramming, and progenitor cell proliferation might be regulated by distinct mechanisms. In conclusion, the careg reporter detects activated MG, and provides a common marker of regeneration-competent cells in diverse zebrafish organs, including the retina. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer JZ declared a shared affiliation with the authors LT and RB to the handling editor at the time of review. (Copyright © 2023 Bise, Pfefferli, Bonvin, Taylor, Lischer, Bruggmann and Jaźwińska.)
Databáze:	MEDLINE
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