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1.
Adv Exp Med Biol ; 1131: 857-879, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31646537

RESUMO

In Drosophila photoreceptor cells, Ca2+ exerts regulatory functions that control the shape, duration, and amplitude of the light response. Ca2+ also orchestrates light adaptation allowing Drosophila to see in light intensity regimes that span several orders of magnitude ranging from single photons to bright sunlight. The prime source for Ca2+ elevation in the cytosol is Ca2+ influx from the extracellular space through light-activated TRP channels. This Ca2+ influx is counterbalanced by constitutive Ca2+ extrusion via the Na+/Ca2+ exchanger, CalX. The light-triggered rise in intracellular Ca2+ exerts its regulatory functions through interaction with about a dozen well-characterized Ca2+ and Ca2+/CaM binding proteins. In this review we will discuss the dynamic changes in Ca2+ concentration upon illumination of photoreceptor cells. We will present the proteins that are known to interact with Ca2+ (/CaM) and elucidate the physiological functions of these interactions.


Assuntos
Cálcio , Drosophila , Células Fotorreceptoras de Invertebrados , Transdução de Sinais , Animais , Antiporters/metabolismo , Cálcio/metabolismo , Drosophila/fisiologia , Proteínas de Drosophila/metabolismo , Luz , Células Fotorreceptoras de Invertebrados/fisiologia
2.
Nature ; 574(7776): 43-44, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31576028
3.
Science ; 365(6460): 1380-1381, 2019 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-31604258
4.
Cell Host Microbe ; 26(3): 301-303, 2019 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-31513766

RESUMO

Because Drosophila larvae do not possess intestinal stem cells, it is unknown how damaged gut cells are replenished. In this issue of Cell Host & Microbe, Houtz et al. (2019) show that larvae have a unique gut repair mechanism that involves borrowing stem cells originally reserved for adult gut formation.


Assuntos
Drosophila , Roubo , Animais , Intestinos , Larva , Células-Tronco
5.
Adv Exp Med Biol ; 1167: 15-35, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31520347

RESUMO

The formation, overgrowth and metastasis of tumors comprise a complex series of cellular and molecular events resulting from the combined effects of a variety of aberrant signaling pathways, mutations, and epigenetic alterations. Modeling this complexity in vivo requires multiple genes to be manipulated simultaneously, which is technically challenging. Here, we analyze how Drosophila research can further contribute to identifying pathways and elucidating mechanisms underlying novel cancer driver (risk) genes associated with tumor growth and metastasis in humans.


Assuntos
Drosophila , Neoplasias , Oncogenes , Animais , Modelos Animais de Doenças , Humanos , Mutação , Transdução de Sinais
6.
Adv Exp Med Biol ; 1167: 37-64, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31520348

RESUMO

Cell competition is an important surveillance mechanism that measures relative fitness between cells in a tissue during development, homeostasis, and disease. Specifically, cells that are "less fit" (losers) are actively eliminated by relatively "more fit" (winners) neighbours, despite the less fit cells otherwise being able to survive in a genetically uniform tissue. Originally described in the epithelial tissues of Drosophila larval imaginal discs, cell competition has since been shown to occur in other epithelial and non-epithelial Drosophila tissues, as well as in mammalian model systems. Many genes and signalling pathways have been identified as playing conserved roles in the mechanisms of cell competition. Among them are genes required for the establishment and maintenance of apico-basal cell polarity: the Crumbs/Stardust/Patj (Crb/Sdt/Patj), Bazooka/Par-6/atypical Protein Kinase C (Baz/Par-6/aPKC), and Scribbled/Discs large 1/Lethal (2) giant larvae (Scrib/Dlg1/L(2)gl) modules. In this chapter, we describe the concepts and mechanisms of cell competition, with emphasis on the relationship between cell polarity proteins and cell competition, particularly the Scrib/Dlg1/L(2)gl module, since this is the best described module in this emerging field.


Assuntos
Polaridade Celular , Transformação Celular Neoplásica , Proteínas de Drosophila , Drosophila , Animais , Modelos Animais de Doenças
7.
Adv Exp Med Biol ; 1167: 113-127, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31520352

RESUMO

The resurgence of Drosophila as a recognized model for carcinogenesis has contributed greatly to our conceptual advance and mechanistic understanding of tumor growth in vivo. With its powerful genetics, Drosophila has emerged as a prime model organism to study cell biology and physiological functions of autophagy. This has enabled exploration of the contributions of autophagy in several tumor models. Here we review the literature of autophagy related to tumorigenesis in Drosophila. Functional analysis of core autophagy components does not provide proof for a classical tumor suppression role for autophagy alone. Autophagy both serve to suppress or support tumor growth. These effects are context-specific, depending on cell type and oncogenic or tumor suppressive lesion. Future delineation of how autophagy impinges on tumorigenesis will demand to untangle in detail, the regulation and flux of autophagy in the respective tumor models. The downstream tumor-regulative roles of autophagy through organelle homeostasis, metabolism, selective autophagy or alternative mechanisms remain largely unexplored.


Assuntos
Autofagia , Carcinogênese , Drosophila , Animais , Modelos Animais de Doenças
8.
Adv Exp Med Biol ; 1167: 157-173, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31520354

RESUMO

MiRNAs are post-transcriptional regulators of gene expression which have been implicated in virtually all biological processes. MiRNAs are frequently dysregulated in human cancers. However, the functional consequences of aberrant miRNA levels are not well understood. Drosophila is emerging as an important in vivo tumor model, especially in the identification of novel cancer genes. Here, we review Drosophila studies which functionally dissect the roles of miRNAs in tumorigenesis. Ultimately, these advances help to understand the implications of miRNA dysregulation in human cancers.


Assuntos
Drosophila , MicroRNAs/genética , Neoplasias/genética , Animais , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica , Humanos , Oncogenes
9.
Adv Exp Med Biol ; 1167: 175-190, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31520355

RESUMO

Accumulative studies suggest that a fraction of cells within a tumor, known as cancer stem cells (CSCs) that initiate tumors, show resistance to most of the therapies, and causes tumor recurrence and metastasis. CSCs could be either transformed normal stem cells or reprogrammed differentiated cells. The eventual goal of CSC research is to identify pathways that selectively regulate CSCs and then target these pathways to eradicate CSCs. CSCs and normal stem cells share some common features, such as self-renewal, the production of differentiated progeny, and the expression of stem-cell markers, however, CSCs vary from normal stem cells in forming tumors. Specifically, CSCs are normally resistant to standard therapies. In addition, CSCs and non-CSCs can be mutually convertible in response to different signals or microenvironments. Even though CSCs are involved in human cancers, the biology of CSCs, is still not well understood, there are urgent needs to study CSCs in model organisms. In the last several years, discoveries in Drosophila have greatly contributed to our understanding of human cancer. Stem-cell tumors in Drosophila share various properties with human CSCs and maybe used to understand the biology of CSCs. In this chapter, we first briefly review CSCs in mammalian systems, then discuss stem-cell tumors in the Drosophila posterior midgut and Malpighian tubules (kidney) and their unique properties as revealed by studying oncogenic Ras protein (RasV12)-transformed stem-cell tumors in the Drosophila kidney and dominant-negative Notch (NDN)-transformed stem-cell tumors in the Drosophila intestine. At the end, we will discuss potential approaches to eliminate CSCs and achieve tumor regression. In future, by screening adult Drosophila neoplastic stem-cell tumor models, we hope to identify novel and efficacious compounds for the treatment of human cancers.


Assuntos
Drosophila , Neoplasias/patologia , Células-Tronco Neoplásicas/citologia , Animais , Diferenciação Celular , Modelos Animais de Doenças , Humanos , Microambiente Tumoral
10.
Adv Exp Med Biol ; 1167: 191-205, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31520356

RESUMO

In humans, cancer-associated cachexia is a complex syndrome that reduces the overall quality of life and survival of cancer patients, particularly for those undergoing chemotherapy. The most easily observable sign of cachexia is organ wasting, the dramatic loss of skeletal muscle and adipose tissue mass. Estimates suggest that 80% of patients in advanced stages of cancer show signs of the syndrome and about 20% of cancer patients die directly of cachexia. Because there is no treatment or drug available to ameliorate organ wasting induced by cancer, cachexia is a relevant clinical problem. However, it is unclear how cachexia is mediated, what factors drive interactions between tumors and host tissues, and which markers of cachexia might be used to allow early detection before the observable signs of organ wasting. In this chapter, we review the current mammalian models of cachexia and the need to use new models of study. We also explain recent developments in Drosophila as a model for studying organ wasting induced by tumors and how fly studies can help unravel important mechanisms that drive cachexia. In particular, we discuss what lessons have been learned from tumor models recently reported to induce systemic organ wasting in Drosophila.


Assuntos
Caquexia/patologia , Drosophila , Neoplasias/patologia , Animais , Modelos Animais de Doenças , Humanos , Músculo Esquelético/patologia , Qualidade de Vida
11.
Adv Exp Med Biol ; 1167: 237-248, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31520359

RESUMO

In recent years, there has been growing interest in using Drosophila for drug discovery as it provides a unique opportunity to screen small molecules against complex disease phenotypes in a whole animal setting. Furthermore, gene-compound interaction experiments that combine compound feeding with complex genetic manipulations enable exploration of compound mechanisms of response and resistance to an extent that is difficult to achieve in other experimental models. Here, I discuss how compound screening and testing approaches reported in Drosophila fit into the current cancer drug discovery pipeline. I then propose a framework for a Drosophila-based cancer drug discovery strategy which would allow the Drosophila research community to effectively leverage the power of Drosophila to identify candidate therapeutics and push our discoveries into the clinic.


Assuntos
Antineoplásicos/farmacologia , Drosophila , Descoberta de Drogas , Neoplasias/tratamento farmacológico , Animais , Modelos Animais de Doenças , Técnicas Genéticas , Fenótipo
12.
Genes Dev ; 33(17-18): 1208-1220, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31416967

RESUMO

The PIWI-interacting RNA (piRNA) pathway is a conserved small RNA-based immune system that protects animal germ cell genomes from the harmful effects of transposon mobilization. In Drosophila ovaries, most piRNAs originate from dual-strand clusters, which generate piRNAs from both genomic strands. Dual-strand clusters use noncanonical transcription mechanisms. Although transcribed by RNA polymerase II, cluster transcripts lack splicing signatures and poly(A) tails. mRNA processing is important for general mRNA export mediated by nuclear export factor 1 (Nxf1). Although UAP56, a component of the transcription and export complex, has been implicated in piRNA precursor export, it remains unknown how dual-strand cluster transcripts are specifically targeted for piRNA biogenesis by export from the nucleus to cytoplasmic processing centers. Here we report that dual-strand cluster transcript export requires CG13741/Bootlegger and the Drosophila nuclear export factor family protein Nxf3. Bootlegger is specifically recruited to piRNA clusters and in turn brings Nxf3. We found that Nxf3 specifically binds to piRNA precursors and is essential for their export to piRNA biogenesis sites, a process that is critical for germline transposon silencing. Our data shed light on how dual-strand clusters compensate for a lack of canonical features of mature mRNAs to be specifically exported via Nxf3, ensuring proper piRNA production.


Assuntos
Transporte Ativo do Núcleo Celular/genética , Proteínas de Drosophila/metabolismo , Drosophila/metabolismo , Precursores de RNA/metabolismo , RNA Interferente Pequeno/metabolismo , Animais , Elementos de DNA Transponíveis/genética , Drosophila/genética , Proteínas de Drosophila/genética
13.
Nat Methods ; 16(8): 750-756, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31363221

RESUMO

The Drosophila wing disc has been a fundamental model system for the discovery of key signaling pathways and for our understanding of developmental processes. However, a complete map of gene expression in this tissue is lacking. To obtain a gene expression atlas in the wing disc, we employed single cell RNA sequencing (scRNA-seq) and developed a method for analyzing scRNA-seq data based on gene expression correlations rather than cell mapping. This enables us to compute expression maps for all detected genes in the wing disc and to discover 824 genes with spatially restricted expression patterns. This approach identifies clusters of genes with similar expression patterns and functional relevance. As proof of concept, we characterize the previously unstudied gene CG5151 and show that it regulates Wnt signaling. Our method will enable the leveraging of scRNA-seq data for generating expression atlases of undifferentiated tissues during development.


Assuntos
Proteínas de Drosophila/genética , Drosophila/genética , Embrião não Mamífero/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Análise de Célula Única/métodos , Asas de Animais/metabolismo , Algoritmos , Animais , Drosophila/embriologia , Embrião não Mamífero/citologia , Feminino , Perfilação da Expressão Gênica , Análise de Sequência de RNA , Asas de Animais/embriologia
14.
Nat Methods ; 16(9): 870-874, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31384047

RESUMO

Light-sheet imaging of cleared and expanded samples creates terabyte-sized datasets that consist of many unaligned three-dimensional image tiles, which must be reconstructed before analysis. We developed the BigStitcher software to address this challenge. BigStitcher enables interactive visualization, fast and precise alignment, spatially resolved quality estimation, real-time fusion and deconvolution of dual-illumination, multitile, multiview datasets. The software also compensates for optical effects, thereby improving accuracy and enabling subsequent biological analysis.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Proteínas de Fluorescência Verde/metabolismo , Processamento de Imagem Assistida por Computador/métodos , Microscopia de Fluorescência/métodos , Software , Animais , Caenorhabditis elegans , Drosophila , Feminino , Imagem Tridimensional/métodos , Camundongos
15.
BMC Bioinformatics ; 20(1): 421, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31409274

RESUMO

BACKGROUND: Ultra-fast pseudo-alignment approaches are the tool of choice in transcript-level RNA sequencing (RNA-seq) analyses. Unfortunately, these methods couple the tasks of pseudo-alignment and transcript quantification. This coupling precludes the direct usage of pseudo-alignment to other expression analyses, including alternative splicing or differential gene expression analysis, without including a non-essential transcript quantification step. RESULTS: In this paper, we introduce a transcriptome segmentation approach to decouple these two tasks. We propose an efficient algorithm to generate maximal disjoint segments given a transcriptome reference library on which ultra-fast pseudo-alignment can be used to produce per-sample segment counts. We show how to apply these maximally unambiguous count statistics in two specific expression analyses - alternative splicing and gene differential expression - without the need of a transcript quantification step. Our experiments based on simulated and experimental data showed that the use of segment counts, like other methods that rely on local coverage statistics, provides an advantage over approaches that rely on transcript quantification in detecting and correctly estimating local splicing in the case of incomplete transcript annotations. CONCLUSIONS: The transcriptome segmentation approach implemented in Yanagi exploits the computational and space efficiency of pseudo-alignment approaches. It significantly expands their applicability and interpretability in a variety of RNA-seq analyses by providing the means to model and capture local coverage variation in these analyses.


Assuntos
Algoritmos , Transcriptoma , Processamento Alternativo , Animais , Área Sob a Curva , Drosophila/genética , Humanos , RNA/química , RNA/metabolismo , Curva ROC , Análise de Sequência de RNA
16.
Cell Prolif ; 52(5): e12656, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31264309

RESUMO

OBJECTIVES: Cell migration has a key role in cancer metastasis, which contributes to drug resistance and tumour recurrence. Better understanding of the mechanisms involved in this process will potentially reveal new drug targets for cancer therapy. Fer is a non-receptor protein tyrosine kinase aberrantly expressed in various human cancers, whereas its role in tumour progression remains elusive. MATERIALS AND METHODS: Transgenic flies and epigenetic analysis were employed to investigate the role of Drosophila Fer (FER) in cell migration and underlying mechanisms. Co-immunoprecipitation assay was used to monitor the interaction between FER and Drosophila JNK (Bsk). The conservation of Fer in regulating JNK signalling was explored in mammalian cancer and non-cancer cells. RESULTS: Overexpression of FER triggered cell migration and activated JNK signalling in the Drosophila wing disc. Upregulation and downregulation in the basal activity of Bsk exacerbated and eliminated FER-mediated migration, respectively. In addition, loss of FER blocked signal transduction of the JNK pathway. Specifically, FER interacted with and promoted the activity of Bsk, which required both the kinase domain and the C-terminal of Bsk. Lastly, Fer regulated JNK activities in mammalian cells. CONCLUSIONS: Our study reveals FER as a positive regulator of JNK-mediated cell migration and suggests its potential role as a therapeutic target for cancer metastasis.


Assuntos
Proteínas de Drosophila/metabolismo , Drosophila/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Proteínas Tirosina Quinases/metabolismo , Animais , Animais Geneticamente Modificados/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proteínas de Drosophila/química , Matriz Extracelular/metabolismo , Regulação da Expressão Gênica , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/química , Metaloproteinase 1 da Matriz/metabolismo , Domínios Proteicos , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Tirosina Quinases/genética , Interferência de RNA , RNA Interferente Pequeno , Transdução de Sinais , Asas de Animais/metabolismo
17.
Nat Neurosci ; 22(9): 1460-1468, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31332373

RESUMO

Goal-directed navigation is thought to rely on the activity of head-direction cells, but how this activity guides moment-to-moment actions remains poorly understood. Here we characterize how heading neurons in the Drosophila central complex guide moment-to-moment navigational behavior. We establish an innate, heading-neuron-dependent, tethered navigational behavior where walking flies maintain a straight trajectory along a specific angular bearing for hundreds of body lengths. While flies perform this task, we use chemogenetics to transiently rotate their neural heading estimate and observe that the flies slow down and turn in a direction that aims to return the heading estimate to the angle it occupied before stimulation. These results support a working model in which the fly brain quantitatively compares an internal estimate of current heading with an internal goal heading and uses the sign and magnitude of the difference to determine which way to turn, how hard to turn and how fast to walk forward.


Assuntos
Encéfalo/fisiologia , Neurônios/fisiologia , Navegação Espacial/fisiologia , Animais , Sinais (Psicologia) , Drosophila , Feminino , Orientação Espacial/fisiologia
18.
J Chem Ecol ; 45(7): 626-637, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31257561

RESUMO

Since the first reports of damage by Drosophila suzukii, the spotted-wing Drosophila (SWD), over a decade ago in Europe, widespread efforts have been made to understand both the ecology and the evolution of this insect pest, especially due to its phylogenetic proximity to one of the original model organisms, D. melanogaster. In addition, researchers have sought to find economically viable solutions for the monitoring and management of this agricultural pest, which has now swept across much of Europe, North America and Asia. In a new direction of study, we present an investigation of plant-based chemistry, where we search for natural compounds that are structurally similar to known olfactory cues from parasitoid wasps that in turn are well-described ovipositional avoidance cues for many Drosophila species. Here we test 11 plant species across two plant genera, Nepeta and Actinidia, and while we find iridoid compounds in both, only those odorants from Actinidia are noted to be detected by the insect antenna, and in addition, found to be behaviorally active. Moreover, the Actinidia extracts resulted in oviposition avoidance when they were added to fruit samples in the laboratory. Thus we propose the possible efficacy of these plants or their extracted chemistry as a novel means for establishing a cost-effective integrated pest management strategy towards the control of this pest fly.


Assuntos
Actinidia/química , Produtos Biológicos/química , Drosophila/fisiologia , Controle de Insetos/métodos , Nepeta/química , Actinidia/metabolismo , Actinidia/parasitologia , Animais , Produtos Biológicos/farmacologia , Produtos Agrícolas , Drosophila/efeitos dos fármacos , Drosophila/crescimento & desenvolvimento , Cromatografia Gasosa-Espectrometria de Massas , Nepeta/metabolismo , Nepeta/parasitologia , Oviposição/efeitos dos fármacos , Folhas de Planta/química , Folhas de Planta/metabolismo , Folhas de Planta/parasitologia
19.
20.
J Insect Sci ; 19(4)2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31268546

RESUMO

Drosophila suzukii Matsumura (Diptera: Drosophilidae) is currently a major pest management challenge in berry and cherry production. This species has a winter morph phenotype with longer wings and increased melanization associated with survival in colder conditions. Measurements of wing morphology in Michigan D. suzukii collected during 2016 and 2017 showed that induction of this morph began in September and increased into December, correlated with decreasing temperature and day length. Importantly, we found that wing length increases along a continuous scale and there is overlap between the two morph types. We tested whether temperature or photoperiod elicited this phenotypic change using a factorial design with each preadult lifestage held at 10 or 25°C and 16:8 or 8:16 L:D. Our results support temperature as the main driver of transition to the winter morph for all immature stages. Comparing the reproductive capacity of winter morph flies in cold conditions and when previously acclimated to warm conditions, flies with the acclimation experience laid comparable numbers of eggs as the summer morphs at 25°C, indicating that winter morphs can reproduce after surviving cold periods. These results highlight the ability of D. suzukii to adapt to changing temperature conditions, allowing it to survive cold and also exploit warmer periods to build populations when conditions allow.


Assuntos
Aclimatação , Drosophila/fisiologia , Oviposição , Estações do Ano , Asas de Animais/anatomia & histologia , Animais , Drosophila/anatomia & histologia , Feminino , Masculino , Fenótipo , Fotoperíodo , Temperatura Ambiente
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