Myc and Tor drive growth and cell competition in the regeneration blastema of Drosophila wing imaginal discs

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Abstract

During the regeneration of injured or lost tissues, the regeneration blastema serves as a hub for robust growth. Drosophila imaginal discs are a genetically tractable and simple model system for the study of regeneration and organization of this regrowth. Key signals that contribute to regenerative growth in these discs, such as ROS, Wnt/Wg, JNK, p38, JAK/STAT, and the Hippo pathway, have been identified. However, a detailed exploration of the spatial organization of regrowth, the factors that directly drive this growth, and the consequences of activating drivers of regeneration has not been undertaken. Here, we find that regenerative growth in imaginal discs is controlled by the transcription factor Myc and by Tor signaling, which drive proliferation and translation in the regeneration blastema. The spatial organization of growth in the blastema is arranged into concentric growth zones defined by Myc expression, elevated Tor activity, and elevated translation. In addition, the increased Myc expression in the innermost zone induced Xrp1-independent cell competition-like death in the adjacent zones, revealing a delicate balance between driving growth and inducing death in the regenerating tissue. Summary statement Drosophila wing disc regeneration is characterized by concentric growth zones controlled by the Myc transcription factor, the Tor signaling pathway, and Myc-induced cell competition.
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Abstract During the regeneration of injured or lost tissues, the regeneration blastema serves as a hub for robust growth. Drosophila imaginal discs are a genetically tractable and simple model system for the study of regeneration and organization of this regrowth. Key signals that contribute to regenerative growth in these discs, such as ROS, Wnt/Wg, JNK, p38, JAK/STAT, and the Hippo pathway, have been identified. However, a detailed exploration of the spatial organization of regrowth, the factors that directly drive this growth, and the consequences of activating drivers of regeneration has not been undertaken. Here, we find that regenerative growth in imaginal discs is controlled by the transcription factor Myc and by Tor signaling, which drive proliferation and translation in the regeneration blastema. The spatial organization of growth in the blastema is arranged into concentric growth zones defined by Myc expression, elevated Tor activity, and elevated translation. In addition, the increased Myc expression in the innermost zone induced Xrp1-independent cell competition-like death in the adjacent zones, revealing a delicate balance between driving growth and inducing death in the regenerating tissue. Summary statement Drosophila wing disc regeneration is characterized by concentric growth zones controlled by the Myc transcription factor, the Tor signaling pathway, and Myc-induced cell competition. Competing Interest Statement The authors have declared no competing interest. Footnotes This version of the manuscript has been revised to include additional experimental data.

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