Fig. 6: Cell-autonomous sexual identity in enterocytes mediates age-related gut pathology, barrier function and ISC mitoses in response to rapamycin treatment.
a, Feminization of male guts by expression of traF in ECs increased intestinal dysplasia, which was attenuated by rapamycin treatment (200 µM), at 50 days of age (control male mexG4 > + vs feminized male mexG4 > traF; scale bar = 15 µm; n = 7 intestines per condition; two-way ANOVA, interaction P < 0.01; post-hoc test). b, Feminization of male guts by expression of traF in ECs increased gut leakiness (number of Smurfs), which was attenuated by rapamycin treatment (200 µM), at 60 days of age. Bar charts show with n = 10 biological replicates of 6–12 flies per replicate (two-way ANOVA, interaction P < 0.05; post-hoc test). c, Feminization of male guts by expression of traF in ECs increased the number of pH3+ cells, which was attenuated by rapamycin treatment (200 µM), at 20 days of age (n = 15 intestines per condition; two-way ANOVA, interaction P < 0.001; post-hoc test). d, Masculinization of female guts by knockdown of traF in ECs decreased intestinal dysplasia, with no further decrease when combined with rapamycin treatment (200 µM), at 50 days of age (control female mexG4 > + vs masculinized female mexG4 > traF [RNAi]; scale bar = 15 µm; n = 7 intestines per condition; two-way ANOVA, interaction P < 0.01; post-hoc test). e, Masculinization of female guts by knockdown of traF in ECs decreased gut leakiness, which was not further decreased by the combination of rapamycin treatment (200 µM), at 60 days of age. Bar charts show with n = 10 biological replicates of 1,520 flies per replicate (two-way ANOVA, interaction P < 0.001; post-hoc test). f, Masculinization of female guts by knockdown of traF in ECs decreased the number of pH3+ cells, which was further decreased by combination with rapamycin treatment (200 µM), at 20 days of age (n = 15 intestines per condition; two-way ANOVA, interaction P < 0.001; post-hoc test). Data are presented as mean values ± s.e.m.
