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1.
Nat Commun ; 15(1): 1166, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38326318

RESUMO

Drosophila male germline stem cells (GSCs) reside at the tip of the testis and surround a cluster of niche cells. Decapentaplegic (Dpp) is one of the well-established ligands and has a major role in maintaining stem cells located in close proximity. However, the existence and the role of the diffusible fraction of Dpp outside of the niche have been unclear. Here, using genetically-encoded nanobodies called Morphotraps, we physically block Dpp diffusion without interfering with niche-stem cell signaling and find that a diffusible fraction of Dpp is required to ensure differentiation of GSC daughter cells, opposite of its role in maintenance of GSC in the niche. Our work provides an example in which a soluble niche ligand induces opposed cellular responses in stem cells versus in differentiating descendants to ensure spatial control of the niche. This may be a common mechanism to regulate tissue homeostasis.


Assuntos
Proteínas de Drosophila , Animais , Masculino , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Ligantes , Diferenciação Celular/fisiologia , Drosophila/metabolismo , Transdução de Sinais/fisiologia , Nicho de Células-Tronco/fisiologia , Células Germinativas/metabolismo , Drosophila melanogaster/metabolismo
2.
Nat Commun ; 15(1): 1047, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38316749

RESUMO

Chemosensory tissues exhibit significant between-species variability, yet the evolution of gene expression and cell types underlying this diversity remain poorly understood. To address these questions, we conducted transcriptomic analyses of five chemosensory tissues from six Drosophila species and integrated the findings with single-cell datasets. While stabilizing selection predominantly shapes chemosensory transcriptomes, thousands of genes in each tissue have evolved expression differences. Genes that have changed expression in one tissue have often changed in multiple other tissues but at different past epochs and are more likely to be cell type-specific than unchanged genes. Notably, chemosensory-related genes have undergone widespread expression changes, with numerous species-specific gains/losses including novel chemoreceptors expression patterns. Sex differences are also pervasive, including a D. melanogaster-specific excess of male-biased expression in sensory and muscle cells in its forelegs. Together, our analyses provide new insights for understanding evolutionary changes in chemosensory tissues at both global and individual gene levels.


Assuntos
Proteínas de Drosophila , Drosophila melanogaster , Animais , Feminino , Masculino , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Drosophila/genética , Drosophila/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Perfilação da Expressão Gênica , Transcriptoma , Filogenia , Evolução Molecular
3.
BMC Res Notes ; 17(1): 46, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38326892

RESUMO

OBJECTIVE: Neurotransmitters have been extensively studied as neural communication molecules. Genetic associations discovered, and indirect intervention studies in Humans and mammals have led to a general proposition that neurotransmitters have a role in structuring of neuronal network during development. olf413 is a Drosophila gene annotated as coding for dopamine beta-monooxygenase enzyme with a predicted function in octopaminergic pathway. The biological function of this gene is very little worked out. In this study we investigate the requirement of olf413 gene function for octopamine biogenesis and developmental patterning of embryonic nervous system. RESULT: In our study we have used the newly characterized neuronal specific allele olf413SG1.1, and the gene disruption strain olf413MI02014 to dissect out the function of olf413. olf413 has an enhancer activity as depicted by reporter GFP expression, in the embryonic ventral nerve cord, peripheral nervous system and the somatic muscle bundles. Homozygous loss of function mutants show reduced levels of octopamine, and this finding supports the proposed function of the gene in octopamine biogenesis. Further, loss of function of olf413 causes embryonic lethality. FasII staining of these embryos reveal a range of phenotypes in the central and peripheral motor nerves, featuring axonal growth, pathfinding, branching and misrouting defects. Our findings are important as they implicate a key functional requirement of this gene in precise axonal patterning events, a novel developmental role imparted for an octopamine biosynthesis pathway gene in structuring of embryonic nervous system.


Assuntos
Proteínas de Drosophila , Drosophila melanogaster , Animais , Humanos , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Octopamina/metabolismo , Drosophila/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Axônios , Neurotransmissores/metabolismo , Mamíferos/metabolismo
4.
Methods Mol Biol ; 2762: 3-16, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38315356

RESUMO

Hantaviruses, are rodent-borne viruses found worldwide that are transmitted to humans through inhalation of contaminated excreta. They can cause a renal or a pulmonary syndrome, depending on the virus, and no effective treatment is currently available for either of these diseases. Hantaviral particles are covered by a protein lattice composed of two glycoproteins (Gn and Gc) that mediate adsorption to target cells and fusion with endosomal membranes, making them prime targets for neutralizing antibodies. Here we present the methodology to produce soluble recombinant glycoproteins in different conformations, either alone or as a stabilized Gn/Gc complex, using stably transfected Drosophila S2 cells.


Assuntos
Orthohantavírus , Vírus de RNA , Humanos , Animais , Drosophila melanogaster/metabolismo , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/metabolismo , Glicoproteínas/metabolismo
5.
Int J Mol Sci ; 25(3)2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38338731

RESUMO

CTP synthase (CTPS), the rate-limiting enzyme in the de novo synthesis of CTP, assembles into a filamentous structure termed the cytoophidium. The Hippo pathway regulates cell proliferation and apoptosis. The relationship of the nucleotide metabolism with the Hippo pathway is little known. Here, we study the impact of the Hippo pathway on the cytoophidium in Drosophila melanogaster posterior follicle cells (PFCs). We find that the inactivation of the Hippo pathway correlates with reduced cytoophidium length and number within PFCs. During the overexpression of CTPS, the presence of Hippo mutations also reduces the length of cytoophidia in PFCs. In addition, we observe that knocking down CTPS mitigates hpo (Hippo)-associated over-proliferation. In summary, our results suggest that there is a connection between the Hippo pathway and the nucleotide biosynthesis enzyme CTPS in PFCs.


Assuntos
Proteínas de Drosophila , Drosophila , Animais , Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Via de Sinalização Hippo , Citoesqueleto/metabolismo , Nucleotídeos/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
6.
Sci Rep ; 14(1): 3602, 2024 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-38351116

RESUMO

Reproductive success requires the development of viable oocytes and the accurate segregation of chromosomes during meiosis. Failure to segregate chromosomes properly can lead to infertility, miscarriages, or developmental disorders. A variety of factors contribute to accurate chromosome segregation and oocyte development, such as spindle assembly and sister chromatid cohesion. However, many proteins required for meiosis remain unknown. In this study, we aimed to develop a screening pipeline for identifying novel meiotic and fertility genes using the genome of Drosophila melanogaster. To accomplish this goal, genes upregulated within meiotically active tissues were identified. More than 240 genes with no known function were silenced using RNA interference (RNAi) and the effects on meiosis and fertility were assessed. We identified 94 genes that when silenced caused infertility and/or high levels of chromosomal nondisjunction. The vast majority of these genes have human and mouse homologs that are also poorly studied. Through this screening process, we identified novel genes that are crucial for meiosis and oocyte development but have not been extensively studied in human or model organisms. Understanding the function of these genes will be an important step towards the understanding of their biological significance during reproduction.


Assuntos
Proteínas de Drosophila , Infertilidade , Humanos , Animais , Camundongos , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Transcriptoma , Proteínas de Ciclo Celular/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Meiose/genética , Segregação de Cromossomos , Fertilidade/genética , Infertilidade/metabolismo , Oócitos/metabolismo
7.
Life Sci Alliance ; 7(5)2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38373798

RESUMO

Ciliary defects cause several ciliopathies, some of which have late onset, suggesting cilia are actively maintained. Still, we have a poor understanding of the mechanisms underlying their maintenance. Here, we show Drosophila melanogaster IFT88 (DmIFT88/nompB) continues to move along fully formed sensory cilia. We further identify Inactive, a TRPV channel subunit involved in Drosophila hearing and negative-gravitaxis behaviour, and a yet uncharacterised Drosophila Guanylyl Cyclase 2d (DmGucy2d/CG34357) as DmIFT88 cargoes. We also show DmIFT88 binding to the cyclase´s intracellular part, which is evolutionarily conserved and mutated in several degenerative retinal diseases, is important for the ciliary localisation of DmGucy2d. Finally, acute knockdown of both DmIFT88 and DmGucy2d in ciliated neurons of adult flies caused defects in the maintenance of cilium function, impairing hearing and negative-gravitaxis behaviour, but did not significantly affect ciliary ultrastructure. We conclude that the sensory ciliary function underlying hearing in the adult fly requires an active maintenance program which involves DmIFT88 and at least two of its signalling transmembrane cargoes, DmGucy2d and Inactive.


Assuntos
Proteínas de Drosophila , Drosophila , Animais , Drosophila/metabolismo , Cílios/metabolismo , Drosophila melanogaster/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Audição
8.
Development ; 151(3)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38345326

RESUMO

Morphogen gradients provide essential positional information to gene networks through their spatially heterogeneous distribution, yet how they form is still hotly contested, with multiple models proposed for different systems. Here, we focus on the transcription factor Bicoid (Bcd), a morphogen that forms an exponential gradient across the anterior-posterior (AP) axis of the early Drosophila embryo. Using fluorescence correlation spectroscopy we find there are spatial differences in Bcd diffusivity along the AP axis, with Bcd diffusing more rapidly in the posterior. We establish that such spatially varying differences in Bcd dynamics are sufficient to explain how Bcd can have a steep exponential gradient in the anterior half of the embryo and yet still have an observable fraction of Bcd near the posterior pole. In the nucleus, we demonstrate that Bcd dynamics are impacted by binding to DNA. Addition of the Bcd homeodomain to eGFP::NLS qualitatively replicates the Bcd concentration profile, suggesting this domain regulates Bcd dynamics. Our results reveal how a long-range gradient can form while retaining a steep profile through much of its range.


Assuntos
Proteínas de Drosophila , Proteínas de Homeodomínio , Animais , Padronização Corporal/genética , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Embrião não Mamífero/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Transativadores/genética , Transativadores/metabolismo
9.
Proc Natl Acad Sci U S A ; 121(9): e2312784121, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38381783

RESUMO

The onset of apoptosis is characterized by a cascade of caspase activation, where initiator caspases are activated by a multimeric adaptor complex known as the apoptosome. In Drosophila melanogaster, the initiator caspase Dronc undergoes autocatalytic activation in the presence of the Dark apoptosome. Despite rigorous investigations, the activation mechanism for Dronc remains elusive. Here, we report the cryo-EM structures of an auto-inhibited Dark monomer and a single-layered, multimeric Dark/Dronc complex. Our biochemical analysis suggests that the auto-inhibited Dark oligomerizes upon binding to Dronc, which is sufficient for the activation of both Dark and Dronc. In contrast, the previously observed double-ring Dark apoptosome may represent a non-functional or "off-pathway" conformation. These findings expand our understanding on the molecular mechanism of apoptosis in Drosophila.


Assuntos
Proteínas de Drosophila , Drosophila melanogaster , Animais , Drosophila melanogaster/metabolismo , Proteínas de Drosophila/metabolismo , Apoptossomas/química , Drosophila/metabolismo , Caspases/metabolismo
10.
Life Sci ; 340: 122485, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38311220

RESUMO

AIM: Aging is a process characterized by a time-dependent decline in the functionality of adult stem cells and is closely associated with age-related diseases. However, understanding how aging promotes disease and its underlying causes is critical for combating aging. MAIN METHODS: The offspring of UAS-Gal4 and CG12744RNAiDrosophila were cultured for 33 days to evaluate the role of CG12744 in the aging intestine. Immunofluorescence was performed to detect specific cell type markers for assessing proliferation and differentiation. qRT-PCR was used to observe the changes in signaling regulating intestinal homeostasis in the aging intestine after CG12744 knockdown. 16S rRNA-seq analysis was also conducted to elucidate the role of gut microbes in CG12744-mediated intestinal dysfunction. KEY FINDINGS: The mRNA levels of CG12744 were significantly increased in the aged midguts. Knockdown of CG12744 in progenitor cells further exacerbates the age-related intestinal hyperplasia and dysfunction. In particular, upon depletion of CG12744 in progenitors, enteroblasts (EBs) exhibited an increased propensity to differentiate along the enteroendocrine cell (EE) lineage. In contrast, the overexpression of CG12744 in progenitor cells restrained age-related gut hyperplasia in Drosophila. Moreover, CG12744 prevented age-related intestinal stem cell (ISC) overproliferation and differentiation by modulating the EGFR, JNK, and BMP pathways. In addition, the inhibition of CG12744 resulted in a significant increase in the gut microbial composition in aging flies. SIGNIFICANCE: This study established a role for the CG12744 in regulating the proliferation and differentiation of adult stem cells, thereby identifying a potential therapeutic target for diseases caused by age-related dysfunction stem cell dysfunction.


Assuntos
Proteínas de Ligação a DNA , Proteínas de Drosophila , Drosophila , Animais , Diferenciação Celular , Proliferação de Células , Drosophila/genética , Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Receptores ErbB/metabolismo , Hiperplasia/metabolismo , Intestinos , RNA Ribossômico 16S/metabolismo , Células-Tronco , Dedos de Zinco , Proteínas de Ligação a DNA/metabolismo
11.
Mol Biol Evol ; 41(2)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38364113

RESUMO

Evolutionary analyses have estimated that ∼60% of nucleotides in intergenic regions of the Drosophila melanogaster genome are functionally relevant, suggesting that regulatory information may be encoded more densely in intergenic regions than has been revealed by most functional dissections of regulatory DNA. Here, we approached this issue through a functional dissection of the regulatory region of the gene shavenbaby (svb). Most of the ∼90 kb of this large regulatory region is highly conserved in the genus Drosophila, though characterized enhancers occupy a small fraction of this region. By analyzing the regulation of svb in different contexts of Drosophila development, we found that the regulatory information that drives svb expression in the abdominal pupal epidermis is organized in a different way than the elements that drive svb expression in the embryonic epidermis. While in the embryonic epidermis svb is activated by compact enhancers separated by large inactive DNA regions, svb expression in the pupal epidermis is driven by regulatory information distributed over broader regions of svb cis-regulatory DNA. In the same vein, we observed that other developmental genes also display a dense distribution of putative regulatory elements in their regulatory regions. Furthermore, we found that a large percentage of conserved noncoding DNA of the Drosophila genome is contained within regions of open chromatin. These results suggest that part of the evolutionary constraint on noncoding DNA of Drosophila is explained by the density of regulatory information, which may be greater than previously appreciated.


Assuntos
Proteínas de Drosophila , Drosophila , Animais , Drosophila/metabolismo , Fatores de Transcrição/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , DNA , DNA Intergênico/genética , DNA Intergênico/metabolismo , Elementos Facilitadores Genéticos
12.
Aging (Albany NY) ; 16(3): 2005-2025, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38329439

RESUMO

Adult stem cells are pivotal for maintaining tissue homeostasis, and their functional decline is linked to aging and its associated diseases, influenced by the niche cells' environment. Age- and cancer-related reduction of vitamin D and its receptor levels are well documented in human clinical studies. However, the mechanisms through which the vitamin D/vitamin D receptor pathway contributes to anti-aging and extends life expectancy are not well understood. In this study, we aimed to determine the protective role of the vitamin D/vitamin D receptor pathway in differentiated enterocytes (ECs) during intestinal stem cell (ISC) aging. By utilizing a well- established Drosophila midgut model for stem cell aging biology, we revealed that vitamin D receptor knockdown in ECs induced ISC proliferation, EC death, ISC aging, and enteroendocrine cell differentiation. Additionally, age- and oxidative stress-induced increases in ISC proliferation and centrosome amplification were reduced by vitamin D treatment. Our findings suggest a direct evidence of the anti-aging role of the vitamin D/vitamin D receptor pathway and provides insights into the molecular mechanisms underlying healthy aging in Drosophila.


Assuntos
Proteínas de Drosophila , Drosophila , Animais , Humanos , Drosophila/fisiologia , Vitamina D/farmacologia , Vitamina D/metabolismo , Receptores de Calcitriol/genética , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Envelhecimento/metabolismo , Intestinos , Diferenciação Celular/fisiologia , Proliferação de Células , Drosophila melanogaster/metabolismo
13.
Int J Mol Sci ; 25(3)2024 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-38338890

RESUMO

We recently demonstrated that 1,6-hexanediol inhibits the formation of assemblysomes. These membraneless cell organelles have important roles in co-translational protein complex assembly and also store halfway translated DNA damage response proteins for a timely stress response. Recognizing the therapeutic potential of 1,6-hexanediol in dismantling assemblysomes likely to be involved in chemo- or radiotherapy resistance of tumor cells, we initiated an investigation into the properties of 1,6-hexanediol. Our particular interest was to determine if this compound induces DNA double-strand breaks by releasing the BLM helicase. Its yeast ortholog Sgs1 was confirmed to be a component of assemblysomes. The BLM helicase induces DNA damage when overexpressed due to the DNA double-strand breaks it generates during its normal function to repair DNA damage sites. It is evident that storing Sgs1 helicase in assemblysomes is crucial to express the full-length functional protein only in the event of DNA damage. Alternatively, if we dissolve assemblysomes using 1,6-hexanediol, ribosome-nascent chain complexes might become targets of ribosome quality control. We explored these possibilities and found, through the Drosophila wing-spot test assay, that 1,6-hexanediol induces DNA double-strand breaks. Lethality connected to recombination events following 1,6-hexanediol treatment can be mitigated by inducing DNA double-strand breaks with X-ray. Additionally, we confirmed that SMC5 recruits DmBLM to DNA damage sites, as knocking it down abolishes the rescue effect of DNA double-strand breaks on 1,6-hexanediol-induced lethality in Drosophila melanogaster.


Assuntos
DNA Helicases , Proteínas de Drosophila , Drosophila melanogaster , Glicóis , Animais , DNA/metabolismo , DNA Helicases/metabolismo , Reparo do DNA , Drosophila/genética , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Recombinação Homóloga , RecQ Helicases/genética , RecQ Helicases/metabolismo
14.
Cell Rep ; 43(1): 113657, 2024 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-38175752

RESUMO

Environmental factors influence an organism's reproductive ability by regulating germline development and physiology. While the reproductive adaptations in response to extrinsic stress cues offer fitness and survival advantages to individuals, the mechanistic understanding of these modifications remains unclear. Here, we find that parasitoid wasps' stress signaling regulates Drosophila melanogaster oogenesis. We show that fruit flies dwelling in the wasp-infested area elevate their fecundity, and the observed reproductive response is specific to Pachycrepoideus sp., a pupal parasitoid wasp. Pachycrepoideus-specific olfactory and visual cues recruit the signaling pathways that promote germline stem cell proliferation and accelerate follicle development, increasing egg production in Drosophila females. Downregulation of signaling engaged in oocyte development by shifting flies to a non-wasp-infested environment increases apoptosis of the developing follicles. Thus, this study establishes host germline responsiveness to parasitoid-specific signals and supports a predator strategy to increase hosts for infection.


Assuntos
Parasitos , Vespas , Humanos , Animais , Feminino , Drosophila , Drosophila melanogaster/metabolismo , Sinais (Psicologia) , Vespas/fisiologia , Proliferação de Células , Células Germinativas , Interações Hospedeiro-Parasita
15.
Cell Rep ; 43(1): 113640, 2024 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-38180839

RESUMO

Adhesion G-protein-coupled receptors (aGPCRs) form a large family of cell surface molecules with versatile tasks in organ development. Many aGPCRs still await their functional and pharmacological deorphanization. Here, we characterized the orphan aGPCR CG11318/mayo of Drosophila melanogaster and found it expressed in specific regions of the gastrointestinal canal and anal plates, epithelial specializations that control ion homeostasis. Genetic removal of mayo results in tachycardia, which is caused by hyperkalemia of the larval hemolymph. The hyperkalemic effect can be mimicked by a raise in ambient potassium concentration, while normal potassium levels in mayoKO mutants can be restored by pharmacological inhibition of potassium channels. Intriguingly, hyperkalemia and tachycardia are caused non-cell autonomously through mayo-dependent control of enterocyte proliferation in the larval midgut, which is the primary function of this aGPCR. These findings characterize the ancestral aGPCR Mayo as a homeostatic regulator of gut development.


Assuntos
Drosophila , Hiperpotassemia , Animais , Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Larva/metabolismo , Potássio/metabolismo , Taquicardia , Adesão Celular
16.
Fly (Austin) ; 18(1): 2306687, 2024 12.
Artigo em Inglês | MEDLINE | ID: mdl-38286464

RESUMO

Parkinson's disease (PD), the most prevalent type of parkinsonism, is a progressive neurodegenerative condition marked by several non-motor and motor symptoms. PD is thought to have a complex aetiology that includes a combination of age, genetic predisposition, and environmental factors. Increased expression of α-synuclein (α-Syn) protein is central to the evolvement of neuropathology in this devastating disorder, but the potential of ribose-cysteine and levodopa in abating pathophysiologic changes in PD model is unknown. Crosses were set up between flies conditionally expressing a pathological variant of human α-Syn (UAS-α-Syn) and those expressing GAL4 in neurons (elav-GAL4) to generate offspring referred to as PD flies. Flies were randomly assigned to five groups (n = 40) from the total population of flies, with each group having five replicates. Groups of PD flies were treated with either 500 mg/kg ribose-cysteine diet, 250 mg/kg levodopa diet, or a combination of the two compounds for 21 days, whereas the control group (w1118) and the PD group were exposed to a diet without ribose-cysteine or levodopa. In addition to various biochemical and neurochemical assays, longevity, larval motility, and gravitaxis assays were carried out. Locomotive capability, lifespan, fecundity, antioxidant state, and neurotransmitter systems were all significantly (p < 0.05) compromised by overexpression of α-Syn. However, flies treated both ribose cysteine and levodopa showed an overall marked improvement in motor functions, lifespan, fecundity, antioxidant status, and neurotransmitter system functions. In conclusion, ribose-cysteine and levodopa, both singly and in combination, potentiated a therapeutic effect on alpha-synuclein transgenic Drosophila melanogaster models of Parkinsonism.


Assuntos
Doença de Parkinson , Transtornos Parkinsonianos , Humanos , Animais , Drosophila melanogaster/metabolismo , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo , Levodopa/farmacologia , Levodopa/metabolismo , Cisteína/metabolismo , Ribose , Antioxidantes/metabolismo , Transtornos Parkinsonianos/tratamento farmacológico , Doença de Parkinson/tratamento farmacológico , Neurotransmissores , Oxirredução , Modelos Animais de Doenças
17.
Proc Natl Acad Sci U S A ; 121(3): e2312380120, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38215185

RESUMO

Across internally fertilising species, males transfer ejaculate proteins that trigger wide-ranging changes in female behaviour and physiology. Much theory has been developed to explore the drivers of ejaculate protein evolution. The accelerating availability of high-quality genomes now allows us to test how these proteins are evolving at fine taxonomic scales. Here, we use genomes from 264 species to chart the evolutionary history of Sex Peptide (SP), a potent regulator of female post-mating responses in Drosophila melanogaster. We infer that SP first evolved in the Drosophilinae subfamily and has since followed markedly different evolutionary trajectories in different lineages. Outside of the Sophophora-Lordiphosa, SP exists largely as a single-copy gene with independent losses in several lineages. Within the Sophophora-Lordiphosa, the SP gene family has repeatedly and independently expanded. Up to seven copies, collectively displaying extensive sequence variation, are present in some species. Despite these changes, SP expression remains restricted to the male reproductive tract. Alongside, we document considerable interspecific variation in the presence and morphology of seminal microcarriers that, despite the critical role SP plays in microcarrier assembly in D. melanogaster, appears to be independent of changes in the presence/absence or sequence of SP. We end by providing evidence that SP's evolution is decoupled from that of its receptor, Sex Peptide Receptor, in which we detect no evidence of correlated diversifying selection. Collectively, our work describes the divergent evolutionary trajectories that a novel gene has taken following its origin and finds a surprisingly weak coevolutionary signal between a supposedly sexually antagonistic protein and its receptor.


Assuntos
Proteínas de Drosophila , Drosophila melanogaster , Animais , Feminino , Masculino , Evolução Biológica , Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Proteínas de Drosophila/metabolismo , Peptídeos/genética , Peptídeos/metabolismo , Receptores de Peptídeos/genética , Receptores de Peptídeos/metabolismo , Reprodução/genética , Comportamento Sexual Animal
18.
Biochem Biophys Res Commun ; 695: 149495, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38211532

RESUMO

Piwi and its partner, Piwi-interacting RNA (piRNA), are pivotal in suppressing the harmful effects of transposable elements (TEs) linked to genomic insertional mutagenesis. While primarily active in Drosophila's adult gonadal tissues, causing sterility in its absence, Piwi's role in post-embryonic development remains unclear. Our study reveals Piwi's functional presence in the larval fat body, where it governs developmental growth through systemic insulin/insulin-like growth factor (IGF) signaling (IIS). Piwi knockdown in the fat body resulted in dysregulated TE expression, reduced developmental rate and body growth, and diminished systemic IIS activity. Notably, Piwi knockdown increased Imaginal Morphogenic Protein Late 2 (Imp-L2) expression, akin to insulin-like growth factor-binding protein 7 (IGFBP7), reducing systemic IIS and inhibiting body growth. This unveils a novel role for Piwi in larval adipose tissues, emphasizing its importance in regulating systemic IIS and overall organismal growth.


Assuntos
Proteínas de Drosophila , Drosophila , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina , Animais , Tecido Adiposo/metabolismo , Proteínas Argonautas/genética , Proteínas Argonautas/metabolismo , Elementos de DNA Transponíveis , Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/genética , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo
19.
Development ; 151(3)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38230563

RESUMO

An unanswered question in neurobiology is how are diverse neuron cell types generated from a small number of neural stem cells? In the Drosophila larval central brain, there are eight bilateral Type 2 neuroblast (T2NB) lineages that express a suite of early temporal factors followed by a different set of late temporal factors and generate the majority of the central complex (CX) neurons. The early-to-late switch is triggered by the orphan nuclear hormone receptor Seven-up (Svp), yet little is known about how this Svp-dependent switch is involved in specifying CX neuron identities. Here, we: (1) birth date the CX neurons P-EN and P-FN (early and late, respectively); (2) show that Svp is transiently expressed in all early T2NBs; and (3) show that loss of Svp expands the population of early born P-EN neurons at the expense of late born P-FN neurons. Furthermore, in the absence of Svp, T2NBs fail decommissioning and abnormally extend their lineage into week-old adults. We conclude that Svp is required to specify CX neuron identity, as well as to initiate T2NB decommissioning.


Assuntos
Proteínas de Drosophila , Células-Tronco Neurais , Animais , Fatores de Transcrição/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas de Drosophila/metabolismo , Células-Tronco Neurais/metabolismo , Neurônios/metabolismo , Drosophila/metabolismo , Linhagem da Célula/fisiologia , Drosophila melanogaster/metabolismo
20.
Nucleus ; 15(1): 2304503, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38286757

RESUMO

Adar-mediated adenosine-to-inosine (A-to-I) RNA editing mainly occurs in nucleus and diversifies the transcriptome in a flexible manner. It has been a challenging task to identify beneficial editing sites from the sea of total editing events. The functional Ser>Gly auto-recoding site in insect Adar gene has uneditable Ser codons in ancestral nodes, indicating the selective advantage to having an editable status. Here, we extended this case study to more metazoan species, and also looked for all Drosophila recoding events with potential uneditable synonymous codons. Interestingly, in D. melanogaster, the abundant nonsynonymous editing is enriched in the codons that have uneditable counterparts, but the Adar Ser>Gly case suggests that the editable orthologous codons in other species are not necessarily edited. The use of editable versus ancestral uneditable codon is a smart way to infer the selective advantage of RNA editing, and priority might be given to these editing sites for functional studies due to the feasibility to construct an uneditable allele. Our study proposes an idea to narrow down the candidates of beneficial recoding sites. Meanwhile, we stress that the matched transcriptomes are needed to verify the conservation of editing events during evolution.


Assuntos
Proteínas de Drosophila , RNA , Animais , RNA/genética , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Edição de RNA/genética , Inosina/genética , Códon , Adenosina Desaminase/genética , Adenosina Desaminase/metabolismo , Proteínas de Drosophila/genética
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