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Cell Death and Differentiation Jan 2020The removal of superfluous and unwanted cells is a critical part of animal development. In insects the steroid hormone ecdysone, the focus of this review, is an... (Review)
Review
The removal of superfluous and unwanted cells is a critical part of animal development. In insects the steroid hormone ecdysone, the focus of this review, is an essential regulator of developmental transitions, including molting and metamorphosis. Like other steroid hormones, ecdysone works via nuclear hormone receptors to direct spatial and temporal regulation of gene transcription including genes required for cell death. During insect metamorphosis, pulses of ecdysone orchestrate the deletion of obsolete larval tissues, including the larval salivary glands and the midgut. In this review we discuss the molecular machinery and mechanisms of ecdysone-dependent cell and tissue removal, with a focus on studies in Drosophila and Lepidopteran insects.
Topics: Animals; Cell Death; Drosophila; Ecdysone; Lepidoptera; Metamorphosis, Biological; Molting
PubMed: 31745213
DOI: 10.1038/s41418-019-0456-9 -
Proceedings of the National Academy of... Jun 2022The primary insect steroid hormone ecdysone requires a membrane transporter to enter its target cells. Although an organic anion-transporting polypeptide (OATP) named...
The primary insect steroid hormone ecdysone requires a membrane transporter to enter its target cells. Although an organic anion-transporting polypeptide (OATP) named Ecdysone Importer (EcI) serves this role in the fruit fly and most likely in other arthropod species, this highly conserved transporter is apparently missing in mosquitoes. Here we report three additional OATPs that facilitate cellular incorporation of ecdysone in and the yellow fever mosquito . These additional ecdysone importers (EcI-2, -3, and -4) are dispensable for development and reproduction in , consistent with the predominant role of EcI. In contrast, in , EcI-2 is indispensable for ecdysone-mediated development, whereas EcI-4 is critical for vitellogenesis induced by ecdysone in adult females. Altogether, our results indicate unique and essential functions of these additional ecdysone importers in mosquito development and reproduction, making them attractive molecular targets for species- and stage-specific control of ecdysone signaling in mosquitoes.
Topics: Aedes; Animals; Drosophila; Drosophila melanogaster; Ecdysone; Female; Insect Proteins; Organic Anion Transporters; Vitellogenesis
PubMed: 35696563
DOI: 10.1073/pnas.2202932119 -
The Journal of Experimental Biology Sep 2023Previous studies have shown that selection for starvation resistance in Drosophila melanogaster results in delayed eclosion and increased adult fat stores. It is assumed...
Previous studies have shown that selection for starvation resistance in Drosophila melanogaster results in delayed eclosion and increased adult fat stores. It is assumed that these traits are caused by the starvation selection pressure, but its mechanism is unknown. We found that our starvation-selected (SS) population stores more fat during larval development and has extended larval development and pupal development time. Developmental checkpoints in the third instar associated with ecdysteroid hormone pulses are increasingly delayed. The delay in the late larval period seen in the SS population is indicative of reduced and delayed ecdysone signaling. An enzyme immunoassay for ecdysteroids (with greatest affinity to the metabolically active 20-hydroxyecdysone and the α-ecdysone precursor) confirmed that the SS population had reduced and delayed hormone production compared with that of fed control (FC) flies. Feeding third instar larvae on food supplemented with α-ecdysone partially rescued the developmental delay and reduced subsequent adult starvation resistance. This work suggests that starvation selection causes reduced and delayed production of ecdysteroids in the larval stage and affects the developmental delay phenotype that contributes to subsequent adult fat storage and starvation resistance.
Topics: Animals; Ecdysone; Ecdysteroids; Drosophila melanogaster; Larva; Phenotype
PubMed: 37671530
DOI: 10.1242/jeb.246144 -
International Journal of Molecular... Sep 2022The steroid hormone ecdysone regulates insect development via its nuclear receptor (the EcR protein), which functions as a ligand-dependent transcription factor. The EcR...
The steroid hormone ecdysone regulates insect development via its nuclear receptor (the EcR protein), which functions as a ligand-dependent transcription factor. The EcR regulates target gene expression by binding to ecdysone response elements (EcREs) in their promoter or enhancer regions. Its role in epigenetic regulation and, particularly, in histone acetylation remains to be clarified. Here, we analyzed the dynamics of histone acetylation and demonstrated that the acetylation of histone H3 on lysine 27 (H3K27) at enhancers was required for the transcriptional activation of ecdysone-responsive genes. Western blotting and ChIP-qPCR revealed that ecdysone altered the acetylation of H3K27. For and , ecdysone-responsive genes, enhancer activity, and transcription required the histone acetyltransferase activity of the CBP. EcR binding was critical in inducing enhancer activity and H3K27 acetylation. The CREB-binding protein (CBP) HAT domain catalyzed H3K27 acetylation and CBP coactivation with EcR, independent of the presence of ecdysone. Increased H3K27 acetylation promoted chromatin accessibility, with the EcR and CBP mediating a local chromatin opening in response to ecdysone. Hence, epigenetic mechanisms, including the modification of acetylation and chromatin accessibility, controlled ecdysone-dependent gene transcription.
Topics: Acetylation; CREB-Binding Protein; Chromatin; Ecdysone; Epigenesis, Genetic; Histones; Ligands; Lysine; Transcription Factors; Transcriptional Activation
PubMed: 36142704
DOI: 10.3390/ijms231810791 -
Insect Biochemistry and Molecular... Oct 2022Diapause, a general shutdown of developmental pathways, is a vital adaptation allowing insects to adjust their life cycle to adverse environmental conditions such as...
Time- and temperature-dependent dynamics of prothoracicotropic hormone and ecdysone sensitivity co-regulate pupal diapause in the green-veined white butterfly Pieris napi.
Diapause, a general shutdown of developmental pathways, is a vital adaptation allowing insects to adjust their life cycle to adverse environmental conditions such as winter. Diapause in the pupal stage is regulated by the major developmental hormones prothoracicotropic hormone (PTTH) and ecdysone. Termination of pupal diapause in the butterfly Pieris napi depends on low temperatures; therefore, we study the temperature-dependence of PTTH secretion and ecdysone sensitivity dynamics throughout diapause, with a focus on diapause termination. While PTTH is present throughout diapause in the cell bodies of two pairs of neurosecretory cells in the brain, it is absent in the axons, and the PTTH concentration in the haemolymph is significantly lower during diapause than during post diapause development, indicating that the PTTH signaling is reduced during diapause. The sensitivity of pupae to ecdysone injections is dependent on diapause stage. While pupae are sensitive to ecdysone during early diapause initiation, they gradually lose this sensitivity and become insensitive to non-lethal concentrations of ecdysone about 30 days into diapause. At low temperatures, reflecting natural overwintering conditions, diapause termination propensity after ecdysone injection is precocious compared to controls. In stark contrast, at high temperatures reflecting late summer and early autumn conditions, sensitivity to ecdysone does not return. Thus, here we show that PTTH secretion is reduced during diapause, and additionally, that the low ecdysone sensitivity of early diapause maintenance is lost during termination in a temperature dependent manner. The link between ecdysone sensitivity and low-temperature dependence reveals a putative mechanism of how diapause termination operates in insects that is in line with adaptive expectations for diapause.
Topics: Animals; Butterflies; Diapause; Diapause, Insect; Ecdysone; Insect Hormones; Insecta; Pupa; Temperature
PubMed: 36084800
DOI: 10.1016/j.ibmb.2022.103833 -
Seminars in Cell & Developmental Biology May 2017Over the last decade, microRNAs have emerged as critical regulators in the expression and function of animal genomes. This review article discusses the relationship... (Review)
Review
Over the last decade, microRNAs have emerged as critical regulators in the expression and function of animal genomes. This review article discusses the relationship between microRNA-mediated regulation and the biology of the fruit fly Drosophila melanogaster. We focus on the roles that microRNAs play in tissue growth, germ cell development, hormone action, and the development and activity of the central nervous system. We also discuss the ways in which microRNAs affect robustness. Many gene regulatory networks are robust; they are relatively insensitive to the precise values of reaction constants and concentrations of molecules acting within the networks. MicroRNAs involved in robustness appear to be nonessential under uniform conditions used in conventional laboratory experiments. However, the robust functions of microRNAs can be revealed when environmental or genetic variation otherwise has an impact on developmental outcomes.
Topics: Animals; Cell Differentiation; Central Nervous System; Drosophila Proteins; Drosophila melanogaster; Ecdysone; Female; Gene Expression Regulation, Developmental; Gene Regulatory Networks; Germ Cells; Intercellular Signaling Peptides and Proteins; Male; MicroRNAs; Morphogenesis; Neurons; Protein Isoforms; Signal Transduction; Synapses
PubMed: 27000418
DOI: 10.1016/j.semcdb.2016.03.015 -
Current Opinion in Genetics &... Feb 2024Specifically timed pulses of the moulting hormone ecdysone are necessary for developmental progression in insects, guiding development through important milestones such... (Review)
Review
Specifically timed pulses of the moulting hormone ecdysone are necessary for developmental progression in insects, guiding development through important milestones such as larval moults, pupation and metamorphosis. It also coordinates the acquisition of cell identities, known as cell patterning, and growth in a tissue-specific manner. In the absence of ecdysone, the ecdysone receptor heterodimer Ecdysone Receptor and Ultraspiracle represses expression of target primary response genes, which become de-repressed as the ecdysone titre rises. However, ecdysone signalling elicits both repressive and activating responses in a temporal and tissue-specific manner. To understand how ecdysone achieves such specificity, this review explores the layers of gene regulation involved in stage-appropriate ecdysone responses in Drosophila fruit flies.
Topics: Animals; Drosophila; Ecdysone; Drosophila Proteins; Steroids; Gene Expression Regulation; Larva; Gene Expression Regulation, Developmental; Drosophila melanogaster
PubMed: 38271845
DOI: 10.1016/j.gde.2023.102148 -
Genetics Mar 2023During postembryonic life, hormones, including ecdysteroids, juvenile hormones, insulin-like peptides, and activin/TGFβ ligands act to transform the larval nervous... (Review)
Review
During postembryonic life, hormones, including ecdysteroids, juvenile hormones, insulin-like peptides, and activin/TGFβ ligands act to transform the larval nervous system into an adult version, which is a fine-grained mosaic of recycled larval neurons and adult-specific neurons. Hormones provide both instructional signals that make cells competent to undergo developmental change and timing cues to evoke these changes across the nervous system. While touching on all the above hormones, our emphasis is on the ecdysteroids, ecdysone and 20-hydroxyecdysone (20E). These are the prime movers of insect molting and metamorphosis and are involved in all phases of nervous system development, including neurogenesis, pruning, arbor outgrowth, and cell death. Ecdysteroids appear as a series of steroid peaks that coordinate the larval molts and the different phases of metamorphosis. Each peak directs a stereotyped cascade of transcription factor expression. The cascade components then direct temporal programs of effector gene expression, but the latter vary markedly according to tissue and life stage. The neurons read the ecdysteroid titer through various isoforms of the ecdysone receptor, a nuclear hormone receptor. For example, at metamorphosis the pruning of larval neurons is mediated through the B isoforms, which have strong activation functions, whereas subsequent outgrowth is mediated through the A isoform through which ecdysteroids play a permissive role to allow local tissue interactions to direct outgrowth. The major circulating ecdysteroid can also change through development. During adult development ecdysone promotes early adult patterning and differentiation while its metabolite, 20E, later evokes terminal adult differentiation.
Topics: Animals; Drosophila; Ecdysone; Ecdysteroids; Gene Expression Regulation, Developmental; Larva; Metamorphosis, Biological; Nervous System; Models, Animal
PubMed: 36645270
DOI: 10.1093/genetics/iyac184 -
ELife Mar 2022Cellular ability to mount an enhanced transcriptional response upon repeated exposure to external cues is termed transcriptional memory, which can be maintained...
Cellular ability to mount an enhanced transcriptional response upon repeated exposure to external cues is termed transcriptional memory, which can be maintained epigenetically through cell divisions and can depend on a nuclear pore component Nup98. The majority of mechanistic knowledge on transcriptional memory has been derived from bulk molecular assays. To gain additional perspective on the mechanism and contribution of Nup98 to memory, we used single-molecule RNA FISH (smFISH) to examine the dynamics of transcription in cells upon repeated exposure to the steroid hormone ecdysone. We combined smFISH with mathematical modeling and found that upon hormone exposure, cells rapidly activate a low-level transcriptional response, but simultaneously begin a slow transition into a specialized memory state characterized by a high rate of expression. Strikingly, our modeling predicted that this transition between non-memory and memory states is independent of the transcription stemming from initial activation. We confirmed this prediction experimentally by showing that inhibiting transcription during initial ecdysone exposure did not interfere with memory establishment. Together, our findings reveal that Nup98's role in transcriptional memory is to stabilize the forward rate of conversion from low to high expressing state, and that induced genes engage in two separate behaviors - transcription itself and the establishment of epigenetically propagated transcriptional memory.
Topics: Animals; Drosophila; Drosophila Proteins; Ecdysone; Nuclear Pore; Nuclear Pore Complex Proteins; Transcription, Genetic; Translocation, Genetic
PubMed: 35289742
DOI: 10.7554/eLife.63404 -
The International Journal of... 2015During Drosophila development, the steroid hormone ecdysone plays a key role in the transition from embryo into larva and then into pupa. It is during larval-pupal... (Review)
Review
During Drosophila development, the steroid hormone ecdysone plays a key role in the transition from embryo into larva and then into pupa. It is during larval-pupal metamorphosis that extensive programmed cell death occurs to remove large obsolete larval tissues. During this transition, ecdysone pulses control the expression of specific transcription factors which drive the expression of key genes involved in cell death, thus spatially and temporally controlling programmed cell death. Ecdysone also controls cell death in specific larval and adult tissues. This review focuses on the current knowledge of ecdysone-mediated cell death in Drosophila.
Topics: Animals; Apoptosis; Autophagy; Drosophila; Ecdysone; Gene Expression Regulation, Developmental; Larva; Metamorphosis, Biological; Pupa
PubMed: 26374522
DOI: 10.1387/ijdb.150055sk