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Abstract BackgroundNutrient availability is among the most widespread means by which environmental variability affects developmental outcomes. Because almost all cells within an individual organism share the same genome, structure-specific growth responses must result from changes in gene regulation. Earlier work suggested thathistone deacetylases(HDACs) may serve as epigenetic regulators linking nutritional conditions to trait-specific development. Here we expand on this work by assessing the function of diverseHDACsin the structure-specific growth of both sex-shared and sex-specific traits including evolutionarily novel structures in the horned dung beetleOnthophagus taurus. ResultsWe identified fiveHDACmembers whose downregulation yielded highly variable mortality depending on whichHDACmember was targeted. We then show thatHDAC1,3, and4operate in both a gene- and trait-specific manner in the regulation of nutrition-responsiveness of appendage size and shape. Specifically,HDAC 1, 3,or4knockdown diminished wing size similarly while leg development was differentially affected by RNAi targetingHDAC3andHDAC4. In addition, depletion ofHDAC3transcript resulted in a more rounded shape of genitalia at the pupal stage and decreased the length of adult aedeagus across all body sizes. Most importantly, we find thatHDAC3andHDAC4pattern the morphology and regulate the scaling of evolutionarily novel head and thoracic horns as a function of nutritional variation. ConclusionCollectively, our results suggest that both functional overlap and division of labor amongHDACmembers contribute to morphological diversification of both conventional and recently evolved appendages. More generally, our work raises the possibility thatHDAC-mediated scaling relationships and their evolution may underpin morphological diversification within and across insect species broadly.