scholarly journals Presenilin-Based Genetic Screens in Drosophila melanogaster Identify Novel Notch Pathway Modifiers

Genetics ◽  
2006 ◽  
Vol 172 (4) ◽  
pp. 2309-2324 ◽  
Author(s):  
Matt B. Mahoney ◽  
Annette L. Parks ◽  
David A. Ruddy ◽  
Stanley Y. K. Tiong ◽  
Hanife Esengil ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Notch Pathway ◽  
Genetic Screens

scholarly journals Genetic Screens for Factors Involved in the Notum Bristle Loss of Interspecific Hybrids Between Drosophila melanogaster and D. simulans

Genetics ◽  
2000 ◽  
Vol 156 (1) ◽  
pp. 269-282
Author(s):  
Toshiyuki Takano-Shimizu
Keyword(s):  
Drosophila Melanogaster ◽  
Interspecific Cross ◽  
Species Variation ◽  
Genetic Screens ◽  
Pure Species ◽  
Epistatic Interactions ◽  
X Chromosomes ◽  
Powerful Means ◽  
Different Populations ◽  
Deficiency Screening

Abstract Interspecific cross is a powerful means to uncover hidden within- and between-species variation in populations. One example is a bristle loss phenotype of hybrids between Drosophila melanogaster and D. simulans, although both the pure species have exactly the same pattern of bristle formation on the notum. There exists a large amount of genetic variability in the simulans populations with respect to the number of missing bristles in hybrids, and the variation is largely attributable to simulans X chromosomes. Using nine molecular markers, I screened the simulans X chromosome for genetic factors that were responsible for the differences between a pair of simulans lines with high (H) and low (L) missing bristle numbers. Together with duplication-rescue experiments, a single major quantitative locus was mapped to a 13F–14F region. Importantly, this region accounted for most of the differences between H and L lines in three other independent pairs, suggesting segregation of H and L alleles at the single locus in different populations. Moreover, a deficiency screening uncovered several regions with factors that potentially cause the hybrid bristle loss due to epistatic interactions with the other factors.

scholarly journals The Drosophila melanogaster Ortholog of RFWD3 Functions Independently of RAD51 During DNA Repair

2020 ◽  
Vol 10 (3) ◽  
pp. 999-1004
Author(s):  
Juan Carvajal-Garcia ◽  
Evan R. Gales ◽  
Dale A. Ramsden ◽  
Jeff Sekelsky
Keyword(s):  
Dna Repair ◽  
Drosophila Melanogaster ◽  
Ring Finger ◽  
Double Strand Breaks ◽  
Specific Gene ◽  
Genetic Screens ◽  
Strand Breaks ◽  
Ancestral Function ◽  
Human Ortholog

Repair of damaged DNA is required for the viability of all organisms. Studies in Drosophila melanogaster, driven by the power of genetic screens, pioneered the discovery and characterization of many genes and pathways involved in DNA repair in animals. However, fewer than half of the alleles identified in these screens have been mapped to a specific gene, leaving a potential for new discoveries in this field. Here we show that the previously uncharacterized mutagen sensitive gene mus302 codes for the Drosophila melanogaster ortholog of the E3 ubiquitin ligase RING finger and WD domain protein 3 (RFWD3). In human cells, RFWD3 promotes ubiquitylation of RPA and RAD51 to facilitate repair of collapsed replication forks and double-strand breaks through homologous recombination. Despite the high similarity in sequence to the human ortholog, our evidence fails to support a role for Mus302 in the repair of these types of damage. Last, we observe that the N-terminal third of RFWD3 is only found in mammals, but not in other vertebrates or invertebrates. We propose that the new N-terminal sequence accounts for the acquisition of a new biological function in mammals that explains the functional differences between the human and the fly orthologs, and that Drosophila Mus302 may retain the ancestral function of the protein.

scholarly journals The study of the regulatory region of the Drosophila melanogaster Notch gene by new methods of directed genome editing

2019 ◽  
Vol 23 (2) ◽  
pp. 199-202
Author(s):  
O. V. Andreyenkov ◽  
E. I. Volkova ◽  
N. G. Andreyenkova ◽  
S. A. Demakov
Keyword(s):  
Drosophila Melanogaster ◽  
Genome Editing ◽  
Regulatory Region ◽  
Polytene Chromosomes ◽  
Notch Pathway ◽  
Hereditary Diseases ◽  
Chromatin State ◽  
Open Chromatin ◽  
New Methods ◽  
Notch Gene

The Notch gene plays a key role in the development of organs and tissues of neuroectodermic origin, including the nervous system. In eukaryotic organisms, the Notch pathway is involved in cell fate determination. The Notch gene was first discovered in Drosophila melanogaster. In mammals, the family of Notch receptors includes four homologues. In humans, mutations in the Notch gene cause several hereditary diseases and carcinogenesis. Studies of the regulatory zone of the Notch gene in D. melanogaster have been conducted for several decades. We review their results and methods. The regulatory zone of the Notch gene is in the region of open chromatin state that corresponds to the 3C6/3C7 interband on the cytological map of polytene chromosomes of D. melanogaster salivary glands. The development of new methods for directed genome editing made it possible to create a system for introducing directed changes into the regulatory zone of the gene. Using the CRISPR/Cas9 system, we obtained a directed 4-kilobase deletion including the 5’-regulatory zone, promoter, and the first exon of the Notch gene and introduced the attP site into the first intron of the Notch gene. This approach enabled targeted changes of the sequence of the regulatory and promoter regions of the gene. Thus, it provided a new powerful tool for studies of Notch gene regulation and the organization of the open chromatin state.

scholarly journals Adherens junction remodeling by the Notch pathway in Drosophila melanogaster oogenesis

2007 ◽  
Vol 177 (1) ◽  
pp. 139-150 ◽  
Author(s):  
Muriel Grammont
Keyword(s):  
Drosophila Melanogaster ◽  
Notch Pathway ◽  
Adherens Junction ◽  
Epithelial Morphogenesis ◽  
Follicular Epithelium ◽  
Main Body ◽  
Cell Morphogenesis ◽  
Follicular Cells ◽  
Epithelial Cadherin ◽  
New Evidence

Identifying genes involved in the control of adherens junction (AJ) remodeling is essential to understanding epithelial morphogenesis. During follicular epithelium development in Drosophila melanogaster, the main body follicular cells (MBFCs) are displaced toward the oocyte and become columnar. Concomitantly, the stretched cells (StCs) become squamous and flatten around the nurse cells. By monitoring the expression of epithelial cadherin and Armadillo, I have discovered that the rate of AJ disassembly between the StCs is affected in follicles with somatic clones mutant for fringe or Delta and Serrate. This results in abnormal StC flattening and delayed MBFC displacement. Additionally, accumulation of the myosin II heavy chain Zipper is delayed at the AJs that require disassembly. Together, my results demonstrate that the Notch pathway controls AJ remodeling between the StCs and that this role is crucial for the timing of MBFC displacement and StC flattening. This provides new evidence that Notch, besides playing a key role in cell differentiation, also controls cell morphogenesis.

scholarly journals Endosomal entry regulates Notch receptor activation in Drosophila melanogaster

2008 ◽  
Vol 180 (4) ◽  
pp. 755-762 ◽  
Author(s):  
Thomas Vaccari ◽  
Han Lu ◽  
Ritu Kanwar ◽  
Mark E. Fortini ◽  
David Bilder
Keyword(s):  
Drosophila Melanogaster ◽  
Notch Pathway ◽  
Receptor Activation ◽  
Notch Receptor ◽  
Animal Development ◽  
Cell Proliferation And Differentiation ◽  
Pathway Activation ◽  
Proliferation And Differentiation ◽  
Low Efficiency ◽  
Endocytic Compartments

Signaling through the transmembrane receptor Notch is widely used throughout animal development and is a major regulator of cell proliferation and differentiation. During canonical Notch signaling, internalization and recycling of Notch ligands controls signaling activity, but the involvement of endocytosis in activation of Notch itself is not well understood. To address this question, we systematically assessed Notch localization, processing, and signaling in a comprehensive set of Drosophila melanogaster mutants that block access of cargo to different endocytic compartments. We find that γ-secretase cleavage and signaling of endogenous Notch is reduced in mutants that impair entry into the early endosome but is enhanced in mutants that increase endosomal retention. In mutants that block endosomal entry, we also uncover an alternative, low-efficiency Notch trafficking route that can contribute to signaling. Our data show that endosomal access of the Notch receptor is critical to achieve physiological levels of signaling and further suggest that altered residence in distinct endocytic compartments could underlie pathologies involving aberrant Notch pathway activation.

scholarly journals A shotgun approach to identify mechanical nociception genes

2016 ◽  
Author(s):  
Melissa G. Christianson ◽  
Stephanie E. Mauthner ◽  
W. Daniel Tracey
Keyword(s):  
Drosophila Melanogaster ◽  
Sensory Neurons ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Single Gene ◽  
Behavioral Responses ◽  
Genetic Screen ◽  
Genetic Screens ◽  
Behavioral Testing ◽  
Shotgun Approach

AbstractThe molecular mechanisms of sensing noxious mechanical force by nociceptive sensory neurons remain poorly understood. Traditional methods for probing mechanical nociception behavioral responses are labor intensive and involve the testing of one animal at a time. This time consuming process of behavioral testing has largely precluded large scale analyses. Indeed, large scale genetic screens that have been performed thus far have been largely restricted to the investigation of ion channel genes [1]. Here we describe a new behavioral assay for mechanical nociception in which tens of animals can be stimulated simultaneously. In this assay, third instar larvae of the genetically tractable organism Drosophila melanogaster are mechanically stimulated with tungsten particles that are fired from a gun. We have used the new assay to carry out a genetic screen in which we investigated the function of 231 nociceptor enriched genes with tissue-specific RNA interference. Targeting of 21 genes resulted in mechanically insensitive phenotypes and targeting of a single gene resulted in a hypersensitive mechanical nociception phenotype. Six of the identified genes were previously uncharacterized and these were named after famed Roman gladiators (Spartacus (CG14186), Commodus (CG1311), Flamma (CG10914), Crixus(CG6685), Spiculus (CG10932), and Verus (CG31324)).

Sign in / Sign up

Export Citation Format

Share Document