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Smith-Bolton, R.

Publications and source records attributed to Smith-Bolton, R..

2 recordsLinked to original sources

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

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 statementDrosophila wing disc regeneration is characterized by concentric growth zones controlled by the Myc transcription factor, the Tor signaling pathway, and Myc-induced cell competition.

developmental biology↗

The pioneer transcription factor Zelda facilitates the exit from regeneration and restoration of patterning in Drosophila

For a damaged tissue to regenerate, the injured site must repair the wound, proliferate, and restore the correct patterning and cell types. We found that Zelda, a pioneer transcription factor largely known for its role in embryonic zygotic genome activation, is dispensable for normal wing development but crucial for wing disc patterning during regeneration. Impairing Zelda function during disc regeneration resulted in adult wings with a plethora of cell fate errors, affecting the veins, margins, and posterior compartment identity. Using CUT&RUN, we identified and validated targets of Zelda including the cell fate genes cut, Delta and achaete, which failed to return to their normal expression patterns upon loss of Zelda. In addition, Zelda controls expression of factors previously established to preserve cell fate during regeneration like taranis and osa, which stabilizes engrailed expression during regeneration, thereby preserving posterior identity. Finally, Zelda ensures proper expression of the integrins encoded by multiple edematous wings and myospheroid during regeneration to prevent blisters in the resuting adult wing. Thus, Zelda is crucial for maintaining cell fate and structural architecture of the regenerating tissue.

developmental biology↗