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Endocrine remodelling of the adult intestine sustains reproduction in Drosophila.

Reiff T, Jacobson J, Cognigni P, Antonello Z, Ballesta E, Tan KJ, Yew JY, Dominguez M, Miguel-Aliaga I - Elife (2015)

Bottom Line: In mothers of many species, changes in key energy-associated internal organs are common yet poorly characterised functionally and mechanistically.In contrast to extant models, organ remodelling does not occur in response to increased nutrient intake and/or offspring demands, but rather precedes them.Our findings identify a metabolically significant paradigm of adult somatic organ remodelling linking hormonal signals, epithelial plasticity, and reproductive output.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Neurociencias, Consejo Superior de Investigaciones Cientificas, Universidad Miguel Hernández, Alicante, Spain.

ABSTRACT
The production of offspring is energetically costly and relies on incompletely understood mechanisms that generate a positive energy balance. In mothers of many species, changes in key energy-associated internal organs are common yet poorly characterised functionally and mechanistically. In this study, we show that, in adult Drosophila females, the midgut is dramatically remodelled to enhance reproductive output. In contrast to extant models, organ remodelling does not occur in response to increased nutrient intake and/or offspring demands, but rather precedes them. With spatially and temporally directed manipulations, we identify juvenile hormone (JH) as an anticipatory endocrine signal released after mating. Acting through intestinal bHLH-PAS domain proteins Methoprene-tolerant (Met) and Germ cell-expressed (Gce), JH signals directly to intestinal progenitors to yield a larger organ, and adjusts gene expression and sterol regulatory element-binding protein (SREBP) activity in enterocytes to support increased lipid metabolism. Our findings identify a metabolically significant paradigm of adult somatic organ remodelling linking hormonal signals, epithelial plasticity, and reproductive output.

No MeSH data available.


Related in: MedlinePlus

Reproductive intestinal remodelling is uncoupled from germline demands and is needed to sustain reproduction.Sterile females carrying the ovoD1 mutation experience the post-mating increase in progenitor proliferation (A, p < 0.001 for w1118 and ovoD1, negative binomial GLM, visualised in C and C′ using the esgReDDM tracing system), gut size increase (B, p < 0.001 for w1118 and ovoD1, t-test), and SREBP reporter activation (D, p < 0.001 for w1118 and p = 0.005 for ovoD1, Mann–Whitney test, visualised in E and E′). The role of intestinal remodelling in enhancing reproductive capacity is confirmed with additional RNA interference lines against the JH receptor gce (chosen because of its larger effect in Figure 4E; F, p = 0.002 between GD11178/+ and Mexts> GD11178, p = 0.008 between Mexts> GD11178 and Mexts/+, p < 0.001 between GD47465/+ and Mexts> GD47465, p = 0.003 between Mexts> GD11178 and Mexts/+, t-test with Holm's correction) and SREBP (G, p = 0.008 between GD37641/+ and Mexts> GD37641, p < 0.001 between GD37640/+ and Mexts> GD37640, t-test). Despite these effect on fecundity, eggs laid by gce, Met, or SREBP RNAi mothers are viable (H and I, mean hatched fraction >0.9 for all groups, p > 0.05 for all relevant comparisons, t-test). See Table 1 for full genotypes.DOI:http://dx.doi.org/10.7554/eLife.06930.009
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fig4s1: Reproductive intestinal remodelling is uncoupled from germline demands and is needed to sustain reproduction.Sterile females carrying the ovoD1 mutation experience the post-mating increase in progenitor proliferation (A, p < 0.001 for w1118 and ovoD1, negative binomial GLM, visualised in C and C′ using the esgReDDM tracing system), gut size increase (B, p < 0.001 for w1118 and ovoD1, t-test), and SREBP reporter activation (D, p < 0.001 for w1118 and p = 0.005 for ovoD1, Mann–Whitney test, visualised in E and E′). The role of intestinal remodelling in enhancing reproductive capacity is confirmed with additional RNA interference lines against the JH receptor gce (chosen because of its larger effect in Figure 4E; F, p = 0.002 between GD11178/+ and Mexts> GD11178, p = 0.008 between Mexts> GD11178 and Mexts/+, p < 0.001 between GD47465/+ and Mexts> GD47465, p = 0.003 between Mexts> GD11178 and Mexts/+, t-test with Holm's correction) and SREBP (G, p = 0.008 between GD37641/+ and Mexts> GD37641, p < 0.001 between GD37640/+ and Mexts> GD37640, t-test). Despite these effect on fecundity, eggs laid by gce, Met, or SREBP RNAi mothers are viable (H and I, mean hatched fraction >0.9 for all groups, p > 0.05 for all relevant comparisons, t-test). See Table 1 for full genotypes.DOI:http://dx.doi.org/10.7554/eLife.06930.009

Mentions: Intestinal remodelling during reproduction could result from increased nutrient intake (O'Brien et al., 2011) or utilisation by the developing offspring. Alternatively, it may occur in preparation for, but be uncoupled from, such nutritional demands. Consistent with the latter idea, the mating-triggered changes in proliferation, midgut size, and SREBP activity are all still apparent in sterile female ovoD1 mutant flies in which egg production is blocked prior to vitellogenesis and which do not increase food intake after mating (Barnes et al., 2008) (Figure 4—figure supplement 1). To investigate the significance of intestinal remodelling, we used several RNAi transgenes to downregulate either the JH receptors or SREBP, which is activated by mating, specifically in adult ECs. In all cases, EC-specific downregulation led to a reduction in the number (but not viability) of eggs produced (Figure 4E,F and Figure 4—figure supplement 1), indicating that JH signalling is required to specifically enhance the quantity (fecundity), but not the quality (viability), of reproductive output. Progenitor cell-specific downregulation may also be expected to reduce fecundity; however, we detected expression of several intestinal progenitor drivers outside the intestine (data not shown), which could affect egg production independently of the intestine. More specific tools will be necessary to resolve this important issue.10.7554/eLife.06930.008Figure 4.Metabolic remodelling of ECs by JH sustains reproduction.


Endocrine remodelling of the adult intestine sustains reproduction in Drosophila.

Reiff T, Jacobson J, Cognigni P, Antonello Z, Ballesta E, Tan KJ, Yew JY, Dominguez M, Miguel-Aliaga I - Elife (2015)

Reproductive intestinal remodelling is uncoupled from germline demands and is needed to sustain reproduction.Sterile females carrying the ovoD1 mutation experience the post-mating increase in progenitor proliferation (A, p < 0.001 for w1118 and ovoD1, negative binomial GLM, visualised in C and C′ using the esgReDDM tracing system), gut size increase (B, p < 0.001 for w1118 and ovoD1, t-test), and SREBP reporter activation (D, p < 0.001 for w1118 and p = 0.005 for ovoD1, Mann–Whitney test, visualised in E and E′). The role of intestinal remodelling in enhancing reproductive capacity is confirmed with additional RNA interference lines against the JH receptor gce (chosen because of its larger effect in Figure 4E; F, p = 0.002 between GD11178/+ and Mexts> GD11178, p = 0.008 between Mexts> GD11178 and Mexts/+, p < 0.001 between GD47465/+ and Mexts> GD47465, p = 0.003 between Mexts> GD11178 and Mexts/+, t-test with Holm's correction) and SREBP (G, p = 0.008 between GD37641/+ and Mexts> GD37641, p < 0.001 between GD37640/+ and Mexts> GD37640, t-test). Despite these effect on fecundity, eggs laid by gce, Met, or SREBP RNAi mothers are viable (H and I, mean hatched fraction >0.9 for all groups, p > 0.05 for all relevant comparisons, t-test). See Table 1 for full genotypes.DOI:http://dx.doi.org/10.7554/eLife.06930.009
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4515472&req=5

fig4s1: Reproductive intestinal remodelling is uncoupled from germline demands and is needed to sustain reproduction.Sterile females carrying the ovoD1 mutation experience the post-mating increase in progenitor proliferation (A, p < 0.001 for w1118 and ovoD1, negative binomial GLM, visualised in C and C′ using the esgReDDM tracing system), gut size increase (B, p < 0.001 for w1118 and ovoD1, t-test), and SREBP reporter activation (D, p < 0.001 for w1118 and p = 0.005 for ovoD1, Mann–Whitney test, visualised in E and E′). The role of intestinal remodelling in enhancing reproductive capacity is confirmed with additional RNA interference lines against the JH receptor gce (chosen because of its larger effect in Figure 4E; F, p = 0.002 between GD11178/+ and Mexts> GD11178, p = 0.008 between Mexts> GD11178 and Mexts/+, p < 0.001 between GD47465/+ and Mexts> GD47465, p = 0.003 between Mexts> GD11178 and Mexts/+, t-test with Holm's correction) and SREBP (G, p = 0.008 between GD37641/+ and Mexts> GD37641, p < 0.001 between GD37640/+ and Mexts> GD37640, t-test). Despite these effect on fecundity, eggs laid by gce, Met, or SREBP RNAi mothers are viable (H and I, mean hatched fraction >0.9 for all groups, p > 0.05 for all relevant comparisons, t-test). See Table 1 for full genotypes.DOI:http://dx.doi.org/10.7554/eLife.06930.009
Mentions: Intestinal remodelling during reproduction could result from increased nutrient intake (O'Brien et al., 2011) or utilisation by the developing offspring. Alternatively, it may occur in preparation for, but be uncoupled from, such nutritional demands. Consistent with the latter idea, the mating-triggered changes in proliferation, midgut size, and SREBP activity are all still apparent in sterile female ovoD1 mutant flies in which egg production is blocked prior to vitellogenesis and which do not increase food intake after mating (Barnes et al., 2008) (Figure 4—figure supplement 1). To investigate the significance of intestinal remodelling, we used several RNAi transgenes to downregulate either the JH receptors or SREBP, which is activated by mating, specifically in adult ECs. In all cases, EC-specific downregulation led to a reduction in the number (but not viability) of eggs produced (Figure 4E,F and Figure 4—figure supplement 1), indicating that JH signalling is required to specifically enhance the quantity (fecundity), but not the quality (viability), of reproductive output. Progenitor cell-specific downregulation may also be expected to reduce fecundity; however, we detected expression of several intestinal progenitor drivers outside the intestine (data not shown), which could affect egg production independently of the intestine. More specific tools will be necessary to resolve this important issue.10.7554/eLife.06930.008Figure 4.Metabolic remodelling of ECs by JH sustains reproduction.

Bottom Line: In mothers of many species, changes in key energy-associated internal organs are common yet poorly characterised functionally and mechanistically.In contrast to extant models, organ remodelling does not occur in response to increased nutrient intake and/or offspring demands, but rather precedes them.Our findings identify a metabolically significant paradigm of adult somatic organ remodelling linking hormonal signals, epithelial plasticity, and reproductive output.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Neurociencias, Consejo Superior de Investigaciones Cientificas, Universidad Miguel Hernández, Alicante, Spain.

ABSTRACT
The production of offspring is energetically costly and relies on incompletely understood mechanisms that generate a positive energy balance. In mothers of many species, changes in key energy-associated internal organs are common yet poorly characterised functionally and mechanistically. In this study, we show that, in adult Drosophila females, the midgut is dramatically remodelled to enhance reproductive output. In contrast to extant models, organ remodelling does not occur in response to increased nutrient intake and/or offspring demands, but rather precedes them. With spatially and temporally directed manipulations, we identify juvenile hormone (JH) as an anticipatory endocrine signal released after mating. Acting through intestinal bHLH-PAS domain proteins Methoprene-tolerant (Met) and Germ cell-expressed (Gce), JH signals directly to intestinal progenitors to yield a larger organ, and adjusts gene expression and sterol regulatory element-binding protein (SREBP) activity in enterocytes to support increased lipid metabolism. Our findings identify a metabolically significant paradigm of adult somatic organ remodelling linking hormonal signals, epithelial plasticity, and reproductive output.

No MeSH data available.


Related in: MedlinePlus