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A large-scale transgenic RNAi screen identifies transcription factors that modulate myofiber size in Drosophila

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Muscle-specific RNAi for screen hits identifies transcription factors that modulate developmental myofiber growth in Drosophila.

(A) Validation of RNAi screen hits via dissection of 3rd instar larvae and confocal imaging of ventral longitudinal VL3 and VL4 body wall skeletal muscles, which have stereotypical sizes. (B) Compared to controls (whiteRNAi and mcherryRNAi), RNAi for screen hits driven in skeletal muscle by Mef2-Gal4 leads to a decrease (atrophy) and an increase (hypertrophy) in the size of VL3 and VL4 skeletal muscles, each consisting of a single myofiber. (C) Quantitation of the cumulative area of VL3 and VL4 muscles from multiple larvae indicates that RNAi for Nurf-38, e(y)1, alien, CG7839, Taf1, MBD-R2, mtTFB2, pdm3, and Dati reduces VL3+VL4 muscle area (atrophy). This indicates that these transcription factors are necessary for optimal myofiber growth during larval development. (D) Conversely, muscle-specific RNAi for Foxo, Cnc, and Deaf1 increases the area of VL3+VL4 muscles (hypertrophy), indicating that these transcription factors limit developmental myofiber growth. N = 12–70 and mean±SD is shown; **P<0.01, ***P<0.001.

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doi: https://doi.org/10.1371/journal.pgen.1009926.g002