Biology subjects

Henstridge, M. A.

Publications and source records attributed to Henstridge, M. A..

3 recordsLinked to original sources

bioRxiv2025

Insulin-like peptides play distinct roles in nutrient-dependent plasticity in Drosophila

The highly conserved insulin signalling pathway regulates growth and development time in response to nutrition across metazoans. The fruit fly, Drosophila melanogaster has eight insulin-like peptides, which are differentially expressed across development time, organs, and with nutritional conditions. However, whether individual insulin-like peptides play specific roles in controlling growth remains unknown. Recent studies have revealed that the ratio of protein to carbohydrates in the diet plays a key role in regulating life history traits, rather than the total caloric content of the diet alone. Furthermore, individual insulin-like peptides vary in their expression profiles according to nutrient conditions. Whether these differences in expression have any functional significance to animal life history traits remains unclear. Here we report that reducing the protein content of the larval diet through macronutrient restriction - where the calories lost from protein dilution are offset by increased carbohydrate content - results in a more pronounced developmental delay compared to caloric restriction - where both protein and carbohydrate concentrations are reduced. We further reveal that these two diet types result in notable differences in the expression levels of Drosophila insulin-like peptides 2, 3 and 5, and observe distinct phenotypic responses of individual insulin-like peptide mutants raised on each diet type. Taken together, our findings highlight the distinct roles of individual insulin-like peptides in regulating growth and development time in response to changes in dietary macronutrients, and provide key insights into the molecular mechanisms controlling nutritional plasticity in Drosophila. ARTICLE SUMMARYThe insulin signaling pathway regulates growth and development in response to nutrition across metazoans. In the fruit fly, Drosophila melanogaster, seven insulin-like peptides have been identified that bind to a single insulin receptor, however their specific roles remain unclear. This study shows that reducing the protein content of the diet in different ways results in striking differences in the expression patterns of insulin-like peptides and different phenotypic responses of individual mutants raised on these diets. Together, these findings highlight the distinct roles insulin-like peptides play in regulating important life history traits in response to changes in dietary macronutrients.

genetics↗

bioRxiv2019

Neuropeptide F receptor acts in the Drosophila prothoracic gland to regulate growth and developmental timing

As juvenile animals grow, their behaviour, physiology, and development need to be matched to environmental conditions to ensure they survive to adulthood. However, we know little about how behaviour and physiology are integrated with development to achieve this outcome. Neuropeptides are prime candidates for achieving this due to their well-known signalling functions in controlling many aspects of behaviour, physiology and development in response to environmental cues. In the growing Drosophila larva, while several neuropeptides have been shown to regulate feeding behaviour, and a handful to regulate growth, it is unclear if any of these play a global role in coordinating feeding behaviour with developmental programs. Here, we demonstrate that Neuropeptide F Receptor (NPFR), best studied as a conserved regulator of feeding behaviour from insects to mammals, also regulates development in Drosophila. Knocking down NPFR in the prothoracic gland, which produces the steroid hormone ecdysone, generates developmental delay and an extended feeding period, resulting in increased body size. We show that these effects are due to decreased ecdysone production, as these animals have reduced expression of ecdysone biosynthesis genes and lower ecdysone titres. Moreover, these phenotypes can be rescued by feeding larvae food supplemented with ecdysone. Further, we show that NPFR negatively regulates the insulin signalling pathway in the prothoracic gland to achieve these effects. Taken together, our data demonstrate that NPFR signalling plays a key role in regulating animal development and may thus play a global role in integrating feeding behaviour and development in Drosophila.

developmental biology↗

bioRxiv2018

Torso-like is a component of the hemolymph and regulates the insulin signalling pathway in Drosophila

In Drosophila key developmental transitions are governed by the steroid hormone ecdysone. A number of neuropeptide-activated signalling pathways control ecdysone production in response to environmental signals, including the insulin signalling pathway, which regulates ecdysone production in response to nutrition. Here, we find that the Membrane Attack Complex/Perforin-like protein Torso-like, best characterised for its role in activating the Torso receptor tyrosine kinase in early embryo patterning, also regulates the insulin signalling pathway in Drosophila. We previously reported that the small body size and developmental delay phenotypes of torso-like null mutants resemble those observed when insulin signalling is reduced. Here we report that, in addition to growth defects, torso-like mutants also display metabolic and nutritional plasticity phenotypes characteristic of mutants with impaired insulin signalling. We further find that in the absence of torso-like the expression of insulin-like peptides is increased, as is their accumulation in the insulin-producing cells. Finally, we show that Torso-like is a component of the hemolymph and that it is required in the prothoracic gland to control developmental timing and body size. Taken together, our data suggest that the secretion of Torso-like from the prothoracic gland influences the activity of insulin signalling throughout the body in Drosophila.\n\nARTICLE SUMMARYIn many animals distinct developmental transitions are crucial for the coordinated progression from the juvenile stage to adulthood. In Drosophila, the transition from an immature larva into a reproductively mature adult is controlled by the steroid hormone ecdysone. Several neuropeptide-activated signalling pathways, including the insulin signalling pathway, regulate ecdysone production in response to environmental cues. Here we find that the perforin-like protein Torso-like regulates the insulin signalling pathway. We show that Torso-like is secreted into circulation where it acts to influence insulin-like peptide activity, revealing a novel mechanism for the regulation of insulin signalling in Drosophila.

developmental biology↗