Biology subjects

Nassel, D.

Publications and source records attributed to Nassel, D..

4 recordsLinked to original sources

bioRxiv2026

Doublesex- mediated regulation of insulin signaling drives sex-specific body growth

Most animals develop sex-biased body sizes driven by sexually divergent plasticity in nutrient-dependent growth. Prior work in Drosophila, implicated the sex-determination gene transformer (tra) in regulation of sex differences in body size. However, tra does not widely mediate sex determination across insects. Thus, the unifying molecular pathway governing female-biased sexual size dimorphism (SSD) remains poorly established in non-drosophilid insects. The rice stem borer Chilo suppressalis, a devastating lepidopteran crop pest, exhibits a robust SSD, offering an ideal system to dissect underlying mechanisms. We report that female-specific splice forms of the sex-determining gene doublesex (Csdsx) are master regulators of female-biased growth. Disruption of the female-specific Csdsx exon 3 via CRISPR knockout or RNA interference drastically reduces female body size and completely erases the SSD. Csilp2, encoding a key insulin-like peptide (ILP2), is selectively upregulated in late-instar female larvae, and female CsDsx proteins directly bind and activate the Csilp2 promoter to boost transcription. Loss-of-function of Csilp2 eliminates the SSD by suppressing female somatic overgrowth. Our results identify a novel regulatory cascade: female-specific Dsx directly stimulates insulin signaling via Csilp2, bridging core sex-determination circuitry and nutrient-dependent body growth control. SignificanceSexual size dimorphism (SSD), widespread across insects with larger females, strongly shapes reproductive fitness. Yet reports on the molecular connection between sex determination and dimorphic growth are scarce. Using a major agricultural pest, the rice stem borer with a prominent female-biased SSD, we show that female-specific Doublesex (dsx) splice variants directly activate the promoter of Insulin-like peptide 2 in late larvae to trigger increased growth. Knocking out either gene in females abolishes the SSD. Our findings thus establish dsx as a novel link connecting sex-determination, insulin signaling and nutrient-dependent body growth.

Developmental Biology↗

bioRxiv2024

Anti-diuretic hormone ITP signals via a guanylate cyclase receptor to modulate systemic homeostasis in Drosophila

Insects have evolved a variety of neurohormones that enable them to maintain their nutrient and osmotic homeostasis. While the identities and functions of various insect metabolic and diuretic hormones have been well-established, the characterization of an anti-diuretic signaling system that is conserved across most insects is still lacking. To address this, here we characterized the ion transport peptide (ITP) signaling system in Drosophila. The Drosophila ITP gene encodes five transcript variants which generate three different peptide isoforms: ITP amidated (ITPa) and two ITP-like (ITPL1 and ITPL2) isoforms. Using a combination of anatomical mapping and single-cell transcriptome analyses, we comprehensively characterized the expression of all three ITP isoforms in the nervous system and peripheral tissues. Our analyses reveal wide-spread expression of ITP isoforms. Moreover, we show that ITPa-producing neurons are activated and release ITPa during dehydration. Further, recombinant Drosophila ITPa inhibits diuretic peptide-induced renal tubule secretion ex vivo, thus confirming its role as an anti-diuretic hormone. Using a phylogenetic-driven approach, an ex vivo secretion assay and a heterologous mammalian cell-based assay, we identified and functionally characterized Gyc76C, a membrane guanylate cyclase, as a bona fide Drosophila ITPa receptor. Thus, recombinant ITPa application leads to increased cGMP production in HEK293T cells expressing Drosophila Gyc76C. Moreover, knockdown of Gyc76C in renal tubules abolishes the inhibitory effect of ITPa on diuretic hormone stimulated secretion. Extensive anatomical mapping of Gyc76C reveals that it is highly expressed in larval and adult tissues associated with osmoregulation (renal tubules and rectum) and metabolic homeostasis (fat body). Consistent with this expression, knockdown of Gyc76C in renal tubules impacts tolerance to osmotic and ionic stresses, whereas knockdown specifically in the fat body impacts feeding, nutrient homeostasis and associated behaviors. We also complement receptor knockdown experiments with ITP knockdown and ITPa overexpression in ITPa-producing neurons. Interestingly, the ITPa-Gyc76C pathway examined here is reminiscent of the atrial natriuretic peptide signaling in mammals. Lastly, we utilized connectomics and single-cell transcriptomics to identify synaptic and paracrine pathways upstream and downstream of ITPa-expressing neurons. Our analysis identifies pathways via which ITP neurons integrate hygrosensory inputs and interact with other homeostatic hormonal pathways. Taken together, our systematic characterization of ITP signaling establishes a tractable system to decipher how a small set of neurons integrates diverse inputs to orchestrate systemic homeostasis in Drosophila.

physiology↗

bioRxiv2020

Cholecystokinin-like Peptide Mediates Satiety by Inhibiting Sugar Attraction

Feeding is essential for animal survival and reproduction and is regulated by both internal states and external stimuli. However, little is known about how internal states influence the perception of external sensory cues that regulate feeding behavior. Here, we investigated the neuronal and molecular mechanisms behind nutritional state-mediated regulation of gustatory perception in control of feeding behavior in the brown planthopper and Drosophila. We found that feeding increases the expression of the cholecystokinin-like peptide, sulfakinin (SK), and the activity of a set of SK-expressing neurons. Starvation elevates the transcription of the sugar receptor Gr64f and SK negatively regulates the expression of Gr64f in both insects. This Gr64f regulation is by direct action of SK neurons on Gr64f-expressing neurons of the proboscis and proleg tarsi that co-express the SK receptor CCKLR-17D3. Our findings thus demonstrate how nutritional state induces peptide signaling to modulate sweet perception and thereby feeding behavior.

neuroscience↗

bioRxiv2020

Impact of high-fat diet on lifespan, metabolism, fecundity and behavioral senescence in Drosophila

Excess consumption of high-fat diet (HFD) is likely to result in obesity and increases the predisposition to associated health disorders. Drosophila melanogaster has emerged as an important model to study the effects of HFD on metabolism, gut function, behavior, and ageing. In this study, we investigated the effects of HFD on physiology and behavior of female flies at different time-points over several weeks. We found that HFD decreases lifespan, and also with age leads to accelerated decline of climbing ability in both virgins and mated flies. In virgins HFD also increased sleep fragmentation with age. Furthermore, long-term exposure to HFD results in elevated adipokinetic hormone (AKH) transcript levels and an enlarged crop with increased lipid stores. We detected no long-term effects of HFD on body mass, or levels of triacylglycerides (TAG), glycogen or glucose, although fecundity was diminished. However, one week of HFD resulted in decreased body mass and elevated TAG levels in mated flies. Finally, we investigated the role of AKH in regulating effects of HFD during aging. Both with normal diet (ND) and HFD, Akh mutant flies displayed increased longevity compared to control flies. However, both mutants and controls showed shortened lifespan on HFD compared to ND. In flies exposed to ND, fecundity is decreased in Akh mutants compared to controls after one week, but increased after three weeks. However, HFD leads to a similar decrease in fecundity in both genotypes after both exposure times. Thus, long-term exposure to HFD increases AKH signaling, impairs lifespan and fecundity and augments age-related behavioral senescence.

neuroscience↗