Interaction Between Hormonal Signaling Pathways in Drosophila melanogaster as Revealed by Genetic Interaction Between Methoprene-tolerant and Broad-Complex

ABSTRACT Two Drosophila tumor necrosis factor receptor-associated factors (TRAF), DTRAF1 and DTRAF2, are proposed to have similar functions with their mammalian counterparts as a signal mediator of cell surface receptors. However, their in vivo functions and related signaling pathways are not fully understood yet. Here, we show that DTRAF1 is an in vivo regulator of c-Jun N-terminal kinase (JNK) pathway in Drosophila melanogaster. Ectopic expression of DTRAF1 in the developing eye induced apoptosis, thereby causing a rough-eye phenotype. Further genetic interaction analyses revealed that the apoptosis in the eye imaginal disc and the abnormal eye morphogenesis induced by DTRAF1 are dependent on JNK and its upstream kinases, Hep and DTAK1. In support of these results, DTRAF1-null mutant showed a remarkable reduction in JNK activity with an impaired development of imaginal discs and a defective formation of photosensory neuron arrays. In contrast, DTRAF2 was demonstrated as an upstream activator of nuclear factor-κB (NF-κB). Ectopic expression of DTRAF2 induced nuclear translocation of two Drosophila NF-κBs, DIF and Relish, consequently activating the transcription of the antimicrobial peptide genes diptericin, diptericin-like protein, and drosomycin. Consistently, the null mutant of DTRAF2 showed immune deficiencies in which NF-κB nuclear translocation and antimicrobial gene transcription against microbial infection were severely impaired. Collectively, our findings demonstrate that DTRAF1 and DTRAF2 play pivotal roles in Drosophila development and innate immunity by differentially regulating the JNK- and the NF-κB-dependent signaling pathway, respectively.

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Targeted Expression of the Class II Phosphoinositide 3-Kinase in Drosophila melanogaster Reveals Lipid Kinase-Dependent Effects on Patterning and Interactions with Receptor Signaling Pathways

Molecular and Cellular Biology ◽

10.1128/mcb.24.2.796-808.2004 ◽

2004 ◽

Vol 24 (2) ◽

pp. 796-808 ◽

Cited By ~ 22

Author(s):

Lindsay K. MacDougall ◽

Mary Elizabeth Gagou ◽

Sally J. Leevers ◽

Ernst Hafen ◽

Michael D. Waterfield

Keyword(s):

Drosophila Melanogaster ◽

Signaling Pathways ◽

Egf Receptor ◽

Adaptor Protein ◽

Class Ii ◽

Notch Receptor ◽

Mitogen Activated Protein Kinase ◽

Class I ◽

Wing Venation ◽

Receptor Signaling

ABSTRACT Phosphoinositide 3-kinases (PI3Ks) can be divided into three distinct classes (I, II, and III) on the basis of their domain structures and the lipid signals that they generate. Functions have been assigned to the class I and class III enzymes but have not been established for the class II PI3Ks. We have obtained the first evidence for a biological function for a class II PI3K by expressing this enzyme during Drosophila melanogaster development and by using deficiencies that remove the endogenous gene. Wild-type and catalytically inactive PI3K_68D transgenes have opposite effects on the number of sensory bristles and on wing venation phenotypes induced by modified epidermal growth factor (EGF) receptor signaling. These results indicate that the endogenous PI3K_68D may act antagonistically to the EGF receptor-stimulated Ras-mitogen-activated protein kinase pathway and downstream of, or parallel to, the Notch receptor. A class II polyproline motif in PI3K_68D can bind the Drk adaptor protein in vitro, primarily via the N-terminal SH3 domain of Drk. Drk may thus be important for the localization of PI3K_68D, allowing it to modify signaling pathways downstream of cell surface receptors. The phenotypes obtained are markedly distinct from those generated by expression of the Drosophila class I PI3K, which affects growth but not pattern formation.

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Comparative approaches to the study of physiology: Drosophila as a physiological tool

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00084.2012 ◽

2013 ◽

Vol 304 (3) ◽

pp. R177-R188 ◽

Cited By ~ 5

Author(s):

Wendi S. Neckameyer ◽

Kathryn J. Argue

Keyword(s):

Gene Expression ◽

Drosophila Melanogaster ◽

Pattern Formation ◽

Signaling Pathways ◽

Human Disease ◽

Cognitive Disorders ◽

Model System ◽

Critical Questions ◽

Developmental Signaling ◽

Shed Light

Numerous studies have detailed the extensive conservation of developmental signaling pathways between the model system, Drosophila melanogaster, and mammalian models, but researchers have also profited from the unique and highly tractable genetic tools available in this system to address critical questions in physiology. In this review, we have described contributions that Drosophila researchers have made to mathematical dynamics of pattern formation, cardiac pathologies, the way in which pain circuits are integrated to elicit responses from sensation, as well as the ways in which gene expression can modulate diverse behaviors and shed light on human cognitive disorders. The broad and diverse array of contributions from Drosophila underscore its translational relevance to modeling human disease.

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Interacting proteins identified by genetic interactions: a missense mutation in alpha-tubulin fails to complement alleles of the testis-specific beta-tubulin gene of Drosophila melanogaster.

Molecular and Cellular Biology ◽

10.1128/mcb.9.3.875 ◽

1989 ◽

Vol 9 (3) ◽

pp. 875-884 ◽

Cited By ~ 24

Author(s):

T S Hays ◽

R Deuring ◽

B Robertson ◽

M Prout ◽

M T Fuller

Keyword(s):

Drosophila Melanogaster ◽

Missense Mutation ◽

Null Allele ◽

Genetic Interaction ◽

Structural Proteins ◽

Interacting Proteins ◽

Tubulin Gene ◽

Beta Tubulin ◽

Gene Encoding ◽

Alpha Tubulin

In this paper we demonstrate that failure to complement between mutations at separate loci can be used to identify genes that encode interacting structural proteins. A mutation (nc33) identified because it failed to complement mutant alleles of the gene encoding the testis-specific beta 2-tubulin of Drosophila melanogaster (B2t) did not map to the B2t locus. We show that this second-site noncomplementing mutation is a missense mutation in alpha-tubulin that results in substitution of methionine in place of valine at amino acid 177. Because alpha- and beta-tubulin form a heterodimer, our results suggest that the genetic interaction, failure to complement, is based on the structural interaction between the protein products of the two genes. Although the nc33 mutation failed to complement a null allele of B2t (B2tn), a deletion of the alpha-tubulin gene to which nc33 mapped complemented B2tn. Thus, the failure to complement appears to require the presence of the altered alpha-tubulin encoded by the nc33 allele, which may act as a structural poison when incorporated into either the tubulin heterodimer or microtubules.

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Interacting proteins identified by genetic interactions: a missense mutation in alpha-tubulin fails to complement alleles of the testis-specific beta-tubulin gene of Drosophila melanogaster

Molecular and Cellular Biology ◽

10.1128/mcb.9.3.875-884.1989 ◽

1989 ◽

Vol 9 (3) ◽

pp. 875-884

Author(s):

T S Hays ◽

R Deuring ◽

B Robertson ◽

M Prout ◽

M T Fuller

Keyword(s):

Drosophila Melanogaster ◽

Missense Mutation ◽

Null Allele ◽

Genetic Interaction ◽

Structural Proteins ◽

Interacting Proteins ◽

Tubulin Gene ◽

Beta Tubulin ◽

Gene Encoding ◽

Alpha Tubulin

In this paper we demonstrate that failure to complement between mutations at separate loci can be used to identify genes that encode interacting structural proteins. A mutation (nc33) identified because it failed to complement mutant alleles of the gene encoding the testis-specific beta 2-tubulin of Drosophila melanogaster (B2t) did not map to the B2t locus. We show that this second-site noncomplementing mutation is a missense mutation in alpha-tubulin that results in substitution of methionine in place of valine at amino acid 177. Because alpha- and beta-tubulin form a heterodimer, our results suggest that the genetic interaction, failure to complement, is based on the structural interaction between the protein products of the two genes. Although the nc33 mutation failed to complement a null allele of B2t (B2tn), a deletion of the alpha-tubulin gene to which nc33 mapped complemented B2tn. Thus, the failure to complement appears to require the presence of the altered alpha-tubulin encoded by the nc33 allele, which may act as a structural poison when incorporated into either the tubulin heterodimer or microtubules.

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Two consecutive microtubule-based epithelial seaming events mediate dorsal closure in the scuttle fly Megaselia abdita

eLife ◽

10.7554/elife.33807 ◽

2018 ◽

Vol 7 ◽

Author(s):

Juan Jose Fraire-Zamora ◽

Johannes Jaeger ◽

Jérôme Solon

Keyword(s):

Drosophila Melanogaster ◽

Signaling Pathways ◽

Genetic Regulation ◽

Dorsal Closure ◽

Evolutionary Transition ◽

Morphogenetic Process ◽

Signaling Regulation ◽

Tissue System ◽

Megaselia Abdita

Evolution of morphogenesis is generally associated with changes in genetic regulation. Here, we report evidence indicating that dorsal closure, a conserved morphogenetic process in dipterans, evolved as the consequence of rearrangements in epithelial organization rather than signaling regulation. In Drosophila melanogaster, dorsal closure consists of a two-tissue system where the contraction of extraembryonic amnioserosa and a JNK/Dpp-dependent epidermal actomyosin cable result in microtubule-dependent seaming of the epidermis. We find that dorsal closure in Megaselia abdita, a three-tissue system comprising serosa, amnion and epidermis, differs in morphogenetic rearrangements despite conservation of JNK/Dpp signaling. In addition to an actomyosin cable, M. abdita dorsal closure is driven by the rupture and contraction of the serosa and the consecutive microtubule-dependent seaming of amnion and epidermis. Our study indicates that the evolutionary transition to a reduced system of dorsal closure involves simplification of the seaming process without changing the signaling pathways of closure progression.

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Miro, a Rho GTPase genetically interacts with Alzheimer's disease-associated genes (Tau, Aβ42 and Appl) in Drosophila melanogaster

Biology Open ◽

10.1242/bio.049569 ◽

2020 ◽

Vol 9 (9) ◽

pp. bio049569 ◽

Cited By ~ 2

Author(s):

Komal Panchal ◽

Anand Krishna Tiwari

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Drosophila Melanogaster ◽

Rho Gtpases ◽

Rho Gtpase ◽

Genetic Interaction ◽

Mitochondrial Dynamics ◽

Ectopic Expression ◽

Mitochondrial Outer Membrane ◽

Disease Associated Genes

ABSTRACTMiro (mitochondrial Rho GTPases), a mitochondrial outer membrane protein, facilitates mitochondrial axonal transport along the microtubules to facilitate neuronal function. It plays an important role in regulating mitochondrial dynamics (fusion and fission) and cellular energy generation. Thus, Miro might be associated with the key pathologies of several neurodegenerative diseases (NDs) including Alzheimer's disease (AD). In the present manuscript, we have demonstrated the possible genetic interaction between Miro and AD-related genes such as Tau, Aβ42 and Appl in Drosophila melanogaster. Ectopic expression of Tau, Aβ42 and Appl induced a rough eye phenotype, defects in phototaxis and climbing activity, and shortened lifespan in the flies. In our study, we have observed that overexpression of Miro improves the rough eye phenotype, behavioral activities (climbing and phototaxis) and ATP level in AD model flies. Further, the improvement examined in AD-related phenotypes was correlated with decreased oxidative stress, cell death and neurodegeneration in Miro overexpressing AD model flies. Thus, the obtained results suggested that Miro genetically interacts with AD-related genes in Drosophila and has the potential to be used as a therapeutic target for the design of therapeutic strategies for NDs.This article has an associated First Person interview with the first author of the paper.

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Headcase is a Repressor of Lamellocyte Fate in Drosophila melanogaster

Genes ◽

10.3390/genes10030173 ◽

2019 ◽

Vol 10 (3) ◽

pp. 173 ◽

Cited By ~ 3

Author(s):

Gergely I. B. Varga ◽

Gábor Csordás ◽

Gyöngyi Cinege ◽

Ferenc Jankovics ◽

Rita Sinka ◽

...

Keyword(s):

Drosophila Melanogaster ◽

Cell Differentiation ◽

Blood Cell ◽

Cell Fate ◽

Blood Cells ◽

Mutational Analysis ◽

Genetic Interaction ◽

Lymph Gland ◽

Loss Of Function ◽

Hematopoietic Stem

Due to the evolutionary conservation of the regulation of hematopoiesis, Drosophila provides an excellent model organism to study blood cell differentiation and hematopoietic stem cell (HSC) maintenance. The larvae of Drosophila melanogaster respond to immune induction with the production of special effector blood cells, the lamellocytes, which encapsulate and subsequently kill the invader. Lamellocytes differentiate as a result of a concerted action of all three hematopoietic compartments of the larva: the lymph gland, the circulating hemocytes, and the sessile tissue. Within the lymph gland, the communication of the functional zones, the maintenance of HSC fate, and the differentiation of effector blood cells are regulated by a complex network of signaling pathways. Applying gene conversion, mutational analysis, and a candidate based genetic interaction screen, we investigated the role of Headcase (Hdc), the homolog of the tumor suppressor HECA in the hematopoiesis of Drosophila. We found that naive loss-of-function hdc mutant larvae produce lamellocytes, showing that Hdc has a repressive role in effector blood cell differentiation. We demonstrate that hdc genetically interacts with the Hedgehog and the Decapentaplegic pathways in the hematopoietic niche of the lymph gland. By adding further details to the model of blood cell fate regulation in the lymph gland of the larva, our findings contribute to the better understanding of HSC maintenance.

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