Myc sustains Regional and Sex-biased Organ Zonation in the Drosophila Intestine

Using adult Drosophila intestines, we combine whole-organ 3D cellular mapping with metabolic profiling to uncover regional differences in enterocyte size and metabolism that vary by sex and genotype. Zonation arises from opposing, region-specific and sex-biased actions of the sex determinant Doublesex (Dsx) and the transcription factor Myc.

In enterocytes, male-specific Dsx suppresses Myc, rendering its expression female-biased. Dsx–Myc antagonism enlarges female enterocytes, increasing their ploidy in specific gut regions. It also drives a female-specific lipid profile, marked by sex-biased expression of a cluster of lipases and selective triacylglycerol storage in the anterior midgut.