Growth control through regulation of insulin signalling by nutrition-activated steroid hormone in Drosophila

Kurt Buhler; Jason Clements; Mattias Winant; Lenz Bolckmans; Veerle Vulsteke; Patrick Callaerts

doi:10.1242/dev.165654

Growth control through regulation of insulin-signaling by nutrition-activated steroid hormone

10.1101/234088 ◽

2017 ◽

Author(s):

Kurt Buhler ◽

Jason Clements ◽

Mattias Winant ◽

Veerle Vulsteke ◽

Patrick Callaerts

Keyword(s):

Insulin Signaling ◽

Growth Regulation ◽

Fat Body ◽

Insulin Signalling ◽

Steroid Hormone ◽

Growth Control ◽

Important Variable ◽

Growth Defects ◽

Insulin Producing Cells ◽

Growth Promoting

AbstractGrowth and maturation are coordinated processes in all animals. Integration of internal cues, such as signalling pathways, with external cues such as nutritional status is paramount for an orderly progression of development in function of growth. In Drosophila, this coordination involves insulin and steroid signalling, but the mechanisms by which this occurs and how they are coordinated are incompletely understood. We show that production of the bioactive 20-hydroxyecdysone by the enzyme Shade in the fat body is a nutrient-dependent process. We demonstrate that during fed conditions, Shade plays a role in growth regulation, as knockdown of shade in the fat body resulted in growth defects and perturbed expression and release of the Drosophila insulin-like peptides from the insulin-producing cells (IPCs). We identify the trachea and IPCs as direct targets through which 20-hydroxyecdysone regulates insulin-signaling. The identification of the trachea-dependent regulation of insulin-signaling exposes an important variable that may have been overlooked in other studies focusing on insulin-signaling in Drosophila. Finally, we show with IPC-specific manipulations that 20E may both be a growth-promoting and growth-inhibiting signal in the IPCs acting through different nuclear receptors. Our findings provide a potentially conserved, novel mechanism by which nutrition can modulate steroid hormone bioactivation, reveal an important caveat of a commonly used transgenic tool to study IPC function and yield further insights as to how steroid and insulin signalling are coordinated during development to regulate growth and developmental timing.

Download Full-text

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

10.1101/2019.12.16.878967 ◽

2019 ◽

Cited By ~ 1

Author(s):

Jade R. Kannangara ◽

Michelle A. Henstridge ◽

Linda M. Parsons ◽

Shu Kondo ◽

Christen K. Mirth ◽

...

Keyword(s):

Body Size ◽

Feeding Behaviour ◽

Insulin Signalling ◽

Steroid Hormone ◽

Prothoracic Gland ◽

Environmental Cues ◽

Feeding Period ◽

Animal Development ◽

Insulin Signalling Pathway ◽

Neuropeptide F

SUMMARYAs 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.

Download Full-text

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

10.1101/264325 ◽

2018 ◽

Author(s):

Michelle A. Henstridge ◽

Lucinda Aulsebrook ◽

Takashi Koyama ◽

Travis K. Johnson ◽

James C. Whisstock ◽

...

Keyword(s):

Body Size ◽

Insulin Signalling ◽

Steroid Hormone ◽

The Body ◽

Signalling Pathway ◽

Prothoracic Gland ◽

Signalling Pathways ◽

Mature Adult ◽

Developmental Transitions ◽

Insulin Signalling Pathway

ABSTRACTIn 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.ARTICLE 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.

Download Full-text

Quantitative EM of gap junction distribution in mutant drosophila wing discs

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100077177 ◽

1983 ◽

Vol 41 ◽

pp. 720-721

Author(s):

J.S. Ryerse

Keyword(s):

Gap Junctions ◽

Growth Control ◽

Intercellular Junctions ◽

Wing Disc ◽

En Bloc ◽

Metabolic Cooperation ◽

Drosophila Wing ◽

Adult Wing ◽

Wing Discs ◽

Wing Pouch

Gap junctions are intercellular junctions found in both vertebrates and invertebrates through which ions and small molecules can pass. Their distribution in tissues could be of critical importance for ionic coupling or metabolic cooperation between cells or for regulating the intracellular movement of growth control and pattern formation factors. Studies of the distribution of gap junctions in mutants which develop abnormally may shed light upon their role in normal development. I report here the distribution of gap junctions in the wing pouch of 3 Drosophila wing disc mutants, vg (vestigial) a cell death mutant, 1(2)gd (lethal giant disc) a pattern abnormality mutant and 1(2)gl (lethal giant larva) a neoplastic mutant and compare these with wildtype wing discs.The wing pouch (the anlagen of the adult wing blade) of a wild-type wing disc is shown in Fig. 1 and consists of columnar cells (Fig. 5) joined by gap junctions (Fig. 6). 14000x EMs of conventionally processed, UA en bloc stained, longitudinally sectioned wing pouches were enlarged to 45000x with a projector and tracings were made on which the lateral plasma membrane (LPM) and gap junctions were marked.

Download Full-text

Ultrastructural features of prognostic significance in human oral cancer

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100123490 ◽

1992 ◽

Vol 50 (1) ◽

pp. 618-619

Author(s):

Karvita B. Ahluwalia ◽

Nidhi Sharma

Keyword(s):

Oral Cancer ◽

Squamous Cell ◽

Common Knowledge ◽

Prognostic Significance ◽

Growth Control ◽

Terminal Differentiation ◽

Squamous Cell Carcinomas ◽

Effective Therapy ◽

Invasive Potential ◽

Biological Behaviour

It is common knowledge that apparently similar tumors often show different responses to therapy. This experience has generated the idea that histologically similar tumors could have biologically distinct behaviour. The development of effective therapy therefore, has the explicit challenge of understanding biological behaviour of a tumor. The question is which parameters in a tumor could relate to its biological behaviour ? It is now recognised that the development of malignancy requires an alteration in the program of terminal differentiation in addition to aberrant growth control. In this study therefore, ultrastructural markers that relate to defective terminal differentiation and possibly invasive potential of cells have been identified in human oral leukoplakias, erythroleukoplakias and squamous cell carcinomas of the tongue.

Download Full-text

Microstructural investigation of surface roughness in MBE-grown AlAs

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100138646 ◽

1995 ◽

Vol 53 ◽

pp. 454-455

Author(s):

R. Rajesh ◽

R. Droopad ◽

C. H. Kuo ◽

R. W. Carpenter ◽

G. N. Maracas

Keyword(s):

Thin Film ◽

Real Time ◽

Growth Control ◽

Native Oxide ◽

Effusion Cell ◽

Surface Oxide Layer ◽

Microstructural Investigation ◽

Mbe Growth ◽

Film Substrate ◽

And Control

Knowledge of material pseudodielectric functions at MBE growth temperatures is essential for achieving in-situ, real time growth control. This allows us to accurately monitor and control thicknesses of the layers during growth. Undesired effusion cell temperature fluctuations during growth can thus be compensated for in real-time by spectroscopic ellipsometry. The accuracy in determining pseudodielectric functions is increased if one does not require applying a structure model to correct for the presence of an unknown surface layer such as a native oxide. Performing these measurements in an MBE reactor on as-grown material gives us this advantage. Thus, a simple three phase model (vacuum/thin film/substrate) can be used to obtain thin film data without uncertainties arising from a surface oxide layer of unknown composition and temperature dependence.In this study, we obtain the pseudodielectric functions of MBE-grown AlAs from growth temperature (650°C) to room temperature (30°C). The profile of the wavelength-dependent function from the ellipsometry data indicated a rough surface after growth of 0.5 μm of AlAs at a substrate temperature of 600°C, which is typical for MBE-growth of GaAs.

Download Full-text