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1.
Adv Exp Med Biol ; 1218: 1-7, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32060868

RESUMO

The attention of science first turned to the gene that later earned the name Notch over a century ago, when the American scientist John S. Dexter discovered in his laboratory at Olivet College the characteristic notched-wing phenotype (a nick or notch in the wingtip) in mutant fruit flies Drosophila melanogaster. At present, it is generally accepted that the Notch pathway governs tissue patterning and many key cell fate decisions and other core processes during embryonic development and in adult tissues. Not surprisingly, a broad variety of independent inherited diseases (including CADASIL, Alagille, Adams-Oliver, and Hajdu-Cheney syndromes) have now convincingly been linked to defective Notch signaling. In the second edition of the book entitled Notch Signaling in Embryology and Cancer, leading researchers provide a comprehensive, highly readable overview on molecular mechanisms of Notch signaling (Volume I), and notch's roles in embryology (Vol. II) and cancer (Vol. III). In these introductory pages of Vol. II, we give a short overview on its individual chapters, which are intended to provide both basic scientists and clinicians who seek today's clearest understanding of the broad role of Notch signaling in embryology with an authoritative day-to-day source.


Assuntos
Padronização Corporal , Receptores Notch/metabolismo , Transdução de Sinais , Animais , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/embriologia , Drosophila melanogaster/metabolismo , Humanos
2.
Adv Exp Med Biol ; 1218: 9-37, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32060869

RESUMO

The evolutionary highly conserved Notch pathway, which first developed during evolution in metazoans and was first discovered in fruit flies (Drosophila melanogaster), governs many core processes including cell fate decisions during embryonic development. A huge mountain of scientific evidence convincingly demonstrates that Notch signaling represents one of the most important pathways that regulate embryogenesis from sponges, roundworms, Drosophila melanogaster, and mice to humans. In this review, we give a brief introduction on how Notch orchestrates the embryonic development of several selected tissues, summarizing some of the most relevant findings in the central nervous system, skin, kidneys, liver, pancreas, inner ear, eye, skeleton, heart, and vascular system.


Assuntos
Desenvolvimento Embrionário , Receptores Notch/metabolismo , Animais , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/embriologia , Drosophila melanogaster/metabolismo , Humanos , Especificidade de Órgãos
3.
Adv Exp Med Biol ; 1218: 39-58, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32060870

RESUMO

During central nervous system (CNS) development, a complex series of events play out, starting with the establishment of neural progenitor cells, followed by their asymmetric division and formation of lineages and the differentiation of neurons and glia. Studies in the Drosophila melanogaster embryonic CNS have revealed that the Notch signal transduction pathway plays at least five different and distinct roles during these events. Herein, we review these many faces of Notch signalling and discuss the mechanisms that ensure context-dependent and compartment-dependent signalling. We conclude by discussing some outstanding issues regarding Notch signalling in this system, which likely have bearing on Notch signalling in many species.


Assuntos
Sistema Nervoso Central/embriologia , Sistema Nervoso Central/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/embriologia , Drosophila melanogaster/metabolismo , Receptores Notch/metabolismo , Transdução de Sinais , Animais
4.
Adv Exp Med Biol ; 1218: 59-75, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32060871

RESUMO

Notch signaling exerts multiple important functions in various developmental processes, including cell differentiation and cell proliferation, while mis-regulation of this pathway results in a variety of complex diseases, such as cancer and developmental defects. The simplicity of the Notch pathway in Drosophila melanogaster, in combination with the availability of powerful genetics, makes this an attractive model for studying the fundamental mechanisms of how Notch signaling is regulated and how it functions in various cellular contexts. Recently, increasing evidence for epigenetic control of Notch signaling reveals the intimate link between epigenetic regulators and Notch signaling pathway. In this chapter, we summarize the research advances of Notch and CAF-1 in Drosophila development and the epigenetic regulation mechanisms of Notch signaling activity by CAF-1 as well as other epigenetic modification machineries, which enables Notch to orchestrate different biological inputs and outputs in specific cellular contexts.


Assuntos
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/embriologia , Drosophila melanogaster/metabolismo , Epigênese Genética , Receptores Notch/metabolismo , Transdução de Sinais/genética , Animais , Drosophila melanogaster/genética
5.
Adv Exp Med Biol ; 1218: 103-127, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32060874

RESUMO

Notch pathway plays diverse and fundamental roles during animal development. One of the most relevant, which arises directly from its unique mode of activation, is the specification of cell fates and tissue boundaries. The development of the leg of Drosophila melanogaster is a fine example of this Notch function, as it is required to specify the fate of the cells that will eventually form the leg joints, the flexible structures that separate the different segments of the adult leg. Notch activity is accurately activated and maintained at the distal end of each segment in response to the proximo-distal patterning gene network of the developing leg. Region-specific downstream targets of Notch in turn regulate the formation of the different types of joints. We discuss recent findings that shed light on the molecular and cellular mechanisms that are ultimately governed by Notch to achieve epithelial fold and joint morphogenesis. Finally, we briefly summarize the role that Notch plays in inducing the nonautonomous growth of the leg. Overall, this book chapter aims to highlight leg development as a useful model to study how patterning information is translated into specific cell behaviors that shape the final form of an adult organ.


Assuntos
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/embriologia , Drosophila melanogaster/metabolismo , Extremidades/embriologia , Morfogênese , Receptores Notch/metabolismo , Transdução de Sinais , Animais
6.
Nat Cell Biol ; 21(11): 1370-1381, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31685997

RESUMO

Cell migration is hypothesized to involve a cycle of behaviours beginning with leading edge extension. However, recent evidence suggests that the leading edge may be dispensable for migration, raising the question of what actually controls cell directionality. Here, we exploit the embryonic migration of Drosophila macrophages to bridge the different temporal scales of the behaviours controlling motility. This approach reveals that edge fluctuations during random motility are not persistent and are weakly correlated with motion. In contrast, flow of the actin network behind the leading edge is highly persistent. Quantification of actin flow structure during migration reveals a stable organization and asymmetry in the cell-wide flowfield that strongly correlates with cell directionality. This organization is regulated by a gradient of actin network compression and destruction, which is controlled by myosin contraction and cofilin-mediated disassembly. It is this stable actin-flow polarity, which integrates rapid fluctuations of the leading edge, that controls inherent cellular persistence.


Assuntos
Actinas/genética , Movimento Celular/genética , Drosophila melanogaster/embriologia , Mecanotransdução Celular , Peixe-Zebra/embriologia , Actinas/metabolismo , Animais , Polaridade Celular , Rastreamento de Células , Cofilina 1/genética , Cofilina 1/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Embrião não Mamífero , Regulação da Expressão Gênica no Desenvolvimento , Genes Reporter , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Hemócitos/citologia , Hemócitos/metabolismo , Queratinócitos/citologia , Queratinócitos/metabolismo , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Macrófagos/citologia , Macrófagos/metabolismo , Miosinas/genética , Miosinas/metabolismo , Cultura Primária de Células , Peixe-Zebra/genética , Peixe-Zebra/metabolismo
7.
PLoS Genet ; 15(10): e1008444, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31589607

RESUMO

Specification of cell identity and the proper functioning of a mature cell depend on precise regulation of gene expression. Both binary ON/OFF regulation of transcription, as well as more fine-tuned control of transcription levels in the ON state, are required to define cell types. The Drosophila melanogaster Hox gene, Ultrabithorax (Ubx), exhibits both of these modes of control during development. While ON/OFF regulation is needed to specify the fate of the developing wing (Ubx OFF) and haltere (Ubx ON), the levels of Ubx within the haltere differ between compartments along the proximal-distal axis. Here, we identify and molecularly dissect the novel contribution of a previously identified Ubx cis-regulatory module (CRM), anterobithorax (abx), to a negative auto-regulatory loop that decreases Ubx expression in the proximal compartment of the haltere as compared to the distal compartment. We find that Ubx, in complex with the known Hox cofactors, Homothorax (Hth) and Extradenticle (Exd), acts through low-affinity Ubx-Exd binding sites to reduce the levels of Ubx transcription in the proximal compartment. Importantly, we also reveal that Ubx-Exd-binding site mutations sufficient to result in de-repression of abx activity in a transgenic context are not sufficient to de-repress Ubx expression when mutated at the endogenous locus, suggesting the presence of multiple mechanisms through which Ubx-mediated repression occurs. Our results underscore the complementary nature of CRM analysis through transgenic reporter assays and genome modification of the endogenous locus; but, they also highlight the increasing need to understand gene regulation within the native context to capture the potential input of multiple genomic elements on gene control.


Assuntos
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Homeodomínio/metabolismo , Homeostase/genética , Fatores de Transcrição/metabolismo , Asas de Animais/embriologia , Animais , Animais Geneticamente Modificados , Sítios de Ligação/fisiologia , Proteínas de Drosophila/genética , Drosophila melanogaster/embriologia , Genes de Insetos/fisiologia , Proteínas de Homeodomínio/genética , Larva/crescimento & desenvolvimento , Mutação , Elementos Reguladores de Transcrição/fisiologia , Fatores de Transcrição/genética
8.
PLoS Pathog ; 15(9): e1007936, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31504075

RESUMO

Wolbachia are the most widespread maternally-transmitted bacteria in the animal kingdom. Their global spread in arthropods and varied impacts on animal physiology, evolution, and vector control are in part due to parasitic drive systems that enhance the fitness of infected females, the transmitting sex of Wolbachia. Male killing is one common drive mechanism wherein the sons of infected females are selectively killed. Despite decades of research, the gene(s) underlying Wolbachia-induced male killing remain unknown. Here using comparative genomic, transgenic, and cytological approaches in fruit flies, we identify a candidate gene in the eukaryotic association module of Wolbachia prophage WO, termed WO-mediated killing (wmk), which transgenically causes male-specific lethality during early embryogenesis and cytological defects typical of the pathology of male killing. The discovery of wmk establishes new hypotheses for the potential role of phage genes in sex-specific lethality, including the control of arthropod pests and vectors.


Assuntos
Prófagos/genética , Prófagos/patogenicidade , Wolbachia/patogenicidade , Wolbachia/virologia , Animais , Animais Geneticamente Modificados , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/fisiologia , Drosophila/embriologia , Drosophila/microbiologia , Drosophila/virologia , Drosophila melanogaster/embriologia , Drosophila melanogaster/microbiologia , Drosophila melanogaster/virologia , Feminino , Genes Letais , Genes Virais , Interações entre Hospedeiro e Microrganismos/genética , Interações entre Hospedeiro e Microrganismos/fisiologia , Masculino , Prófagos/fisiologia , Razão de Masculinidade , Simbiose/genética , Simbiose/fisiologia , Proteínas Virais/genética , Proteínas Virais/fisiologia
9.
PLoS Genet ; 15(9): e1008351, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31527874

RESUMO

Wnt proteins are secreted signaling factors that regulate cell fate specification and patterning decisions throughout the animal kingdom. In the Drosophila wing epithelium, Wingless (Wg, the homolog of Wnt1) is secreted from a narrow strip of cells at the dorsal-ventral boundary. However, the route of Wg secretion in polarized epithelial cells remains poorly understood and key proteins involved in this process are still unknown. Here, we performed an in vivo RNAi screen and identified members of the exocyst complex to be required for apical but not basolateral Wg secretion. Specifically blocking the apical Wg secretion leads to reduced downstream signaling. Using an in vivo 'temporal-rescue' assay, our results further indicate that apically secreted Wg activates target genes that require high signaling activity. In conclusion, our results demonstrate that the exocyst is required for an apical route of Wg secretion from polarized wing epithelial cells.


Assuntos
Proteínas de Drosophila/metabolismo , Via Secretória/fisiologia , Via de Sinalização Wnt/fisiologia , Proteína Wnt1/metabolismo , Animais , Padronização Corporal/genética , Proteínas de Drosophila/fisiologia , Drosophila melanogaster/embriologia , Drosophila melanogaster/genética , Células Epiteliais/metabolismo , Epitélio/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/genética , Ligantes , Transdução de Sinais , Asas de Animais/embriologia , Asas de Animais/metabolismo , Proteínas Wnt/genética , Via de Sinalização Wnt/genética , Proteína Wnt1/genética , Proteína Wnt1/fisiologia
10.
Results Probl Cell Differ ; 67: 277-321, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31435800

RESUMO

The first 3 h of Drosophila melanogaster embryo development are exemplified by rapid nuclear divisions within a large syncytium, transforming the zygote to the cellular blastoderm after 13 successive cleavage divisions. As the syncytial embryo develops, it relies on centrosomes and cytoskeletal dynamics to transport nuclei, maintain uniform nuclear distribution throughout cleavage cycles, ensure generation of germ cells, and coordinate cellularization. For the sake of this review, we classify six early embryo stages that rely on processes coordinated by the centrosome and its regulation of the cytoskeleton. The first stage features migration of one of the female pronuclei toward the male pronucleus following maturation of the first embryonic centrosomes. Two subsequent stages distribute the nuclei first axially and then radially in the embryo. The remaining three stages involve centrosome-actin dynamics that control cortical plasma membrane morphogenesis. In this review, we highlight the dynamics of the centrosome and its role in controlling the six stages that culminate in the cellularization of the blastoderm embryo.


Assuntos
Centrossomo/metabolismo , Drosophila melanogaster/citologia , Drosophila melanogaster/embriologia , Embrião não Mamífero/citologia , Animais , Blastoderma , Núcleo Celular
12.
Nat Commun ; 10(1): 2951, 2019 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-31273212

RESUMO

Epithelial-mesenchymal transition (EMT) is an essential process both in physiological and pathological contexts. Intriguingly, EMT is often associated with tissue invagination during development; however, the impact of EMT on tissue remodeling remain unexplored. Here, we show that at the initiation of the EMT process, cells produce an apico-basal force, orthogonal to the surface of the epithelium, that constitutes an important driving force for tissue invagination in Drosophila. When EMT is ectopically induced, cells starting their delamination generate an orthogonal force and induce ectopic folding. Similarly, during mesoderm invagination, cells undergoing EMT generate an apico-basal force through the formation of apico-basal structures of myosin II. Using both laser microdissection and in silico physical modelling, we show that mesoderm invagination does not proceed if apico-basal forces are impaired, indicating that they constitute driving forces in the folding process. Altogether, these data reveal the mechanical impact of EMT on morphogenesis.


Assuntos
Drosophila melanogaster/embriologia , Transição Epitelial-Mesenquimal , Epitélio/embriologia , Morfogênese , Animais , Polaridade Celular , Simulação por Computador , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/citologia , Drosophila melanogaster/metabolismo , Embrião não Mamífero/citologia , Embrião não Mamífero/metabolismo , Epitélio/metabolismo , Mesoderma/citologia , Mesoderma/embriologia , Mesoderma/metabolismo , Modelos Moleculares , Miosina Tipo II/metabolismo
14.
Mol Biol Cell ; 30(16): 1938-1960, 2019 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-31188739

RESUMO

During morphogenesis, cells must change shape and move without disrupting tissue integrity. This requires cell-cell junctions to allow dynamic remodeling while resisting forces generated by the actomyosin cytoskeleton. Multiple proteins play roles in junctional-cytoskeletal linkage, but the mechanisms by which they act remain unclear. Drosophila Canoe maintains adherens junction-cytoskeletal linkage during gastrulation. Canoe's mammalian homologue Afadin plays similar roles in cultured cells, working in parallel with ZO-1 proteins, particularly at multicellular junctions. We take these insights back to the fly embryo, exploring how cells maintain epithelial integrity when challenged by adherens junction remodeling during germband extension and dorsal closure. We found that Canoe helps cells maintain junctional-cytoskeletal linkage when challenged by the junctional remodeling inherent in mitosis, cell intercalation, and neuroblast invagination or by forces generated by the actomyosin cable at the leading edge. However, even in the absence of Canoe, many cells retain epithelial integrity. This is explained by a parallel role played by the ZO-1 homologue Polychaetoid. In embryos lacking both Canoe and Polychaetoid, cell junctions fail early, with multicellular junctions especially sensitive, leading to widespread loss of epithelial integrity. Our data suggest that Canoe and Polychaetoid stabilize Bazooka/Par3 at cell-cell junctions, helping maintain balanced apical contractility and tissue integrity.


Assuntos
Junções Aderentes/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Células Epiteliais/metabolismo , Proteínas de Junções Íntimas/metabolismo , Animais , Forma Celular , Citoesqueleto/metabolismo , Drosophila melanogaster/embriologia , Desenvolvimento Embrionário , Epiderme/metabolismo , Homeostase , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Morfogênese , Mutação/genética , Fenótipo , Pseudópodes/metabolismo
15.
Nucleic Acids Res ; 47(13): 6842-6857, 2019 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-31175824

RESUMO

Although transposable elements are an important source of regulatory variation, their genome-wide contribution to the transcriptional regulation of stress-response genes has not been studied yet. Stress is a major aspect of natural selection in the wild, leading to changes in the transcriptional regulation of a variety of genes that are often triggered by one or a few transcription factors. In this work, we take advantage of the wealth of information available for Drosophila melanogaster and humans to analyze the role of transposable elements in six stress regulatory networks: immune, hypoxia, oxidative, xenobiotic, heat shock, and heavy metal. We found that transposable elements were enriched for caudal, dorsal, HSF, and tango binding sites in D. melanogaster and for NFE2L2 binding sites in humans. Taking into account the D. melanogaster population frequencies of transposable elements with predicted binding motifs and/or binding sites, we showed that those containing three or more binding motifs/sites are more likely to be functional. For a representative subset of these TEs, we performed in vivo transgenic reporter assays in different stress conditions. Overall, our results showed that TEs are relevant contributors to the transcriptional regulation of stress-response genes.


Assuntos
Elementos de DNA Transponíveis/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Regulação da Expressão Gênica/genética , Genes de Insetos , Estresse Fisiológico/genética , Transcrição Genética/genética , Motivos de Aminoácidos , Animais , Animais Geneticamente Modificados , Translocador Nuclear Receptor Aril Hidrocarboneto/metabolismo , Sítios de Ligação , Imunoprecipitação da Cromatina , Proteínas de Drosophila/genética , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/embriologia , Drosophila melanogaster/imunologia , Feminino , Redes Reguladoras de Genes , Humanos , Fator 2 Relacionado a NF-E2/metabolismo , Ligação Proteica , Especificidade da Espécie , Fatores de Transcrição/metabolismo
16.
PLoS One ; 14(6): e0217906, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31158257

RESUMO

Understanding the transcriptional pathways controlling tissue-specific gene expression is critical to unraveling the complex regulatory networks that underlie developmental mechanisms. Here, we assessed how the Drosophila crossveinless (cv) gene, that encodes a BMP-binding factor, is transcriptionally regulated in the developing embryonic tracheal system. We identify an upstream regulatory region of cv that promotes reporter gene expression in the tracheal precursors. We further demonstrate that this promoter region is directly responsive to the basic, helix-loop-helix-PAS domain factors Trachealess (Trh) and Tango (Tgo), that function to specify tracheal fate. Moreover, cv expression in embryos is lost in trh mutants, and the integrity of the Trh/Tgo binding sites are required for promoter-lacZ expression. These findings for the first time elucidate the transcriptional regulation of one member of a family of BMP binding proteins, that have diverse functions in animal development.


Assuntos
Translocador Nuclear Receptor Aril Hidrocarboneto/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Traqueia/citologia , Fatores de Transcrição/metabolismo , Transcrição Genética , Animais , Animais Geneticamente Modificados , Sequência de Bases , Proteínas de Drosophila/genética , Drosophila melanogaster/embriologia , Drosophila melanogaster/genética , Embrião não Mamífero/citologia , Embrião não Mamífero/metabolismo , Elementos Facilitadores Genéticos/genética , Regulação da Expressão Gênica no Desenvolvimento , Loci Gênicos , Regiões Promotoras Genéticas/genética
17.
Mol Biol (Mosk) ; 53(3): 476-484, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31184613

RESUMO

It is known that long (200-300 nucleotides and longer) non-protein-coding RNAs (ncRNAs) tissue-specifically expressed from the regulatory regions of developmental genes can regulate the transcription of the mRNA of these genes. In this study, an attempt is made to identify differentially expressed ncRNAs in the extended promoter region of the fork head (fkh) gene of the fruit fly Drosophila melanogaster. We investigated four preparations of the total RNA: from embryos, from adult flies (separately from females and males), and from the S2 cell line of cultured Drosophila cells. In the total RNA preparations from embryos and adult flies, the levels of fkh expression differed substantially, whereas in S2 cells its expression is not detected at all (shown in this work). We perform classical Northern blot analysis of gel-separated RNAs hybridized to a series of radioactively labeled DNA fragments corresponding to the adjacent and partially overlapping regions of the promoter region of the fkh gene. Several previously unknown differentially expressed ncRNAs are detected, including those in the regions overlapping with the previously detected regulatory elements (TRE1 and salivary gland enhancer sgE) and the transcription start site of the fkh gene. The collected data complement and clarify the results of the previously conducted RNA-seq experiments, in particular, in terms of the length of the detected RNAs. These results may serve as a foundation for further studies of the mechanisms of tissue-specific regulation of the fkh gene expression.


Assuntos
Northern Blotting , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Fatores de Transcrição Forkhead/genética , Regulação da Expressão Gênica no Desenvolvimento , Regiões Promotoras Genéticas/genética , RNA Longo não Codificante/análise , RNA Longo não Codificante/genética , Animais , Linhagem Celular , Drosophila melanogaster/embriologia , Drosophila melanogaster/crescimento & desenvolvimento , Elementos Facilitadores Genéticos/genética , Feminino , Masculino , Especificidade de Órgãos
18.
PLoS Biol ; 17(5): e2006741, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31086359

RESUMO

Macrophages encounter and clear apoptotic cells during normal development and homeostasis, including at numerous sites of pathology. Clearance of apoptotic cells has been intensively studied, but the effects of macrophage-apoptotic cell interactions on macrophage behaviour are poorly understood. Using Drosophila embryos, we have exploited the ease of manipulating cell death and apoptotic cell clearance in this model to identify that the loss of the apoptotic cell clearance receptor Six-microns-under (Simu) leads to perturbation of macrophage migration and inflammatory responses via pathological levels of apoptotic cells. Removal of apoptosis ameliorates these phenotypes, while acute induction of apoptosis phenocopies these defects and reveals that phagocytosis of apoptotic cells is not necessary for their anti-inflammatory action. Furthermore, Simu is necessary for clearance of necrotic debris and retention of macrophages at wounds. Thus, Simu is a general detector of damaged self and represents a novel molecular player regulating macrophages during resolution of inflammation.


Assuntos
Apoptose , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/citologia , Drosophila melanogaster/metabolismo , Inflamação/patologia , Macrófagos/patologia , Proteínas de Membrana/metabolismo , Animais , Movimento Celular , Proteínas de Drosophila/genética , Drosophila melanogaster/embriologia , Embrião não Mamífero/metabolismo , Proteínas de Membrana/genética , Mutação/genética , Necrose , Fagocitose
19.
Elife ; 82019 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-31140975

RESUMO

Fluorescent transcriptional reporters are widely used as signaling reporters and biomarkers to monitor pathway activities and determine cell type identities. However, a large amount of dynamic information is lost due to the long half-life of the fluorescent proteins. To better detect dynamics, fluorescent transcriptional reporters can be destabilized to shorten their half-lives. However, applications of this approach in vivo are limited due to significant reduction of signal intensities. To overcome this limitation, we enhanced translation of a destabilized fluorescent protein and demonstrate the advantages of this approach by characterizing spatio-temporal changes of transcriptional activities in Drosophila. In addition, by combining a fast-folding destabilized fluorescent protein and a slow-folding long-lived fluorescent protein, we generated a dual-color transcriptional timer that provides spatio-temporal information about signaling pathway activities. Finally, we demonstrate the use of this transcriptional timer to identify new genes with dynamic expression patterns.


Assuntos
Regulação da Expressão Gênica , Transcrição Genética , Animais , Drosophila melanogaster/embriologia , Drosophila melanogaster/genética , Embrião não Mamífero/citologia , Embrião não Mamífero/metabolismo , Elementos Facilitadores Genéticos/genética , Fluorescência , Proteínas de Fluorescência Verde/metabolismo , Intestinos/citologia , Biossíntese de Proteínas , Receptores Notch/metabolismo , Fatores de Transcrição STAT/metabolismo , Células-Tronco/citologia
20.
Mol Biol (Mosk) ; 53(2): 225-239, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31099773

RESUMO

The ensemble of gap genes is one of the best studied and most conserved gene regulatory networks (GRNs). Gap genes, such as hunchback (hb), Krüppel (Kr), pou-domain (pdm; pdm1 and pdm2), and castor (cas) genes belong to the well-known families Ikaros (IKZF1/hb), Krüppel-like factor (KLF/Kr), POU domain (BRN1/pdm-1, BRN2/pdm-2), and Castor homologs (CASZ1/cas), which are present in all vertebrate genomes and code for site-specific transcription factors. Gap genes form a core of an embryonic segmentation control subnetwork and define the temporal identity of neuroblasts in Drosophila embryos. The key gene regulatory mechanisms whereby the gap genes govern segmentation and neurogenesis are similar. Moreover, the gap genes are evolutionarily conserved in terms of their function as a core of the temporal specification GRN during neurogenesis in vertebrates, including humans. A problem of special interest is to understand the extent of conservation for the molecular mechanisms involved in the regulatory functions of the gap genes. The problem is especially important because human orthologs of the gap gens are crucial for many pathophysiological processes, including tumor growth suppression.


Assuntos
Drosophila melanogaster/citologia , Drosophila melanogaster/genética , Evolução Molecular , Redes Reguladoras de Genes , Neurônios/metabolismo , Animais , Drosophila melanogaster/embriologia , Regulação da Expressão Gênica no Desenvolvimento , Fatores de Tempo , Fatores de Transcrição/metabolismo
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