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Matthew C Pahl, Susan E Doyle, Sarah E Siegrist
Most neurogenesis occurs during development, driven by the cell divisions of neural stem cells (NSCs). We use Drosophila to understand how neurogenesis terminates once development is complete, a process critical for neural circuit formation. We identified E93, a steroid-hormone-induced transcription factor that downregulates phosphatidylinositol 3-kinase (PI3K) levels to activate autophagy for elimination of mushroom body (MB) neuroblasts. MB neuroblasts are a subset of Drosophila NSCs that generate neurons important for memory and learning...
February 5, 2019: Current Biology: CB
James C Sears, Woong Jae Choi, Kendal Broadie
Recent work shows Fragile X Mental Retardation Protein (FMRP) drives the translation of very large proteins (>2000 aa) mediating neurodevelopment. Loss of function results in Fragile X syndrome (FXS), the leading heritable cause of intellectual disability (ID) and autism spectrum disorder (ASD). Using the Drosophila FXS disease model, we discover FMRP positively regulates the translation of the very large A-Kinase Anchor Protein (AKAP) Rugose (>3000 aa), homolog of ASD-associated human Neurobeachin (NBEA)...
February 13, 2019: Neurobiology of Disease
Zheng Wu, Ji-Long Liu
CTP synthase (CTPsyn) is a metabolic enzyme essential for the de novo synthesis of CTP the nucleotide. CTPsyn can be compartmented into filamentous structures named cytoophidia. Cytoophidia are conserved in a wide range of species and are highly abundant in Drosophila ovaries. Here we report that cytoophidia elongate upon nutrient deprivation, CTPsyn overexpression or heat shock in Drosophila ovaries. We also show that the curvature of cytoophidia changes during apoptosis. Moreover, cytoophidia can be transported from nurse cells to the oocyte via ring canals...
February 12, 2019: Experimental Cell Research
Rachel Orlomoski, Aaron Bogle, Jeanmarie Loss, Rylee Simons, Jacqueline M Dresch, Robert A Drewell, Donald E Spratt
Homeodomain transcription factors (HD TFs) are a large class of evolutionarily conserved DNA binding proteins that contain a basic 60-amino acid region required for binding to specific DNA sites. In Drosophila melanogaster, many of these HD TFs are expressed in the early embryo and control transcription of target genes in development through interaction with cis-regulatory modules. Previous studies where some of the Drosophila HD TFs were purified required the use of strong denaturants (i.e. 6M urea) and multiple chromatography columns, making the downstream biochemical examination of the isolated protein difficult...
February 7, 2019: Protein Expression and Purification
Munmun Chowdhury, Jie Zhang, Xiao-Xia Xu, Zhen He, Yuzhen Lu, Xu-Sheng Liu, Yu-Feng Wang, Xiao-Qiang Yu
An important innate immune response in Drosophila melanogaster is the production of antimicrobial peptides (AMPs). Expression of AMP genes is mediated by the Toll and immune deficiency (IMD) pathways via NF-κB transcription factors Dorsal, DIF and Relish. Dorsal and DIF act downstream of the Toll pathway, whereas Relish acts in the IMD pathway. Dorsal and DIF are held inactive in the cytoplasm by the IκB protein Cactus, while Relish contains an IκB-like inhibitory domain at the C-terminus. NF-κB factors normally form homodimers and heterodimers to regulate gene expression, but formation of heterodimers between Relish and DIF or Dorsal and the specificity and activity of the three NF-κB homodimers and heterodimers are not well understood...
February 6, 2019: Developmental and Comparative Immunology
Qian Yi, Jinxia Wang, Yaxin Song, Zhenzhen Guo, Shan Lei, Xue Yang, Liangping Li, Caiping Gao, Zhou Zhou
Inflammatory bowel disease (IBD) has been well-documented as a chronic gastrointestinal autoimmune disease, but its etiology remains to be elusive. Ascl2 (achaete-scute complex homologue 2), identified as a homologue of the Drosophila achaete-scute gene, has been shown to play an essential for the pathogenesis of autoimmune diseases and cancers. However, whether it is associated with the pathogenesis of IBD remains unclear. Here, we demonstrated that Ascl2 was greatly down-regulated in human IBD and experimental colitis...
February 2, 2019: Biochemical and Biophysical Research Communications
Orkhon Tsogtbaatar, Jong-Hoon Won, Go-Woon Kim, Jeong-Hoon Han, Young-Kyung Bae, Kyung-Ok Cho
Cell survival is essential for all living organisms to cope against multiple environmental insults. Intercellular signaling between dying and surviving cells plays an important role to ensure compensatory proliferation, preventing tissue loss after environmental stresses. Here, we show that Sol narae (Sona), a Disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) in Drosophila is required for cell survival. sona exhibited a positive genetic interaction with Death-associated inhibitor of apoptosis 1 (Diap1), and a negative genetic interaction with reaper (rpr)...
February 4, 2019: Scientific Reports
Ruimin Li, Yu Huang, Qi Zhang, Hongjian Zhou, Ping Jin, Fei Ma
The miR-317 has been revealed to involve in the reproductive response and the larval ovary morphogenesis of Drosophila. However, whether the miR-317 can also regulate Drosophila innate immune responses, which remains unclear to date. Here we have verified that miR-317 can directly target the 3'UTR of Dif-Rc to down-regulate the expression levels of AMP Drs to negatively control Drosophila Toll immune response in vivo and vitro. Specially, the Dif is an important transcription factor of Toll pathway with four transcripts (Dif-Ra, Dif-Rb, Dif-Rc and Dif-Rd)...
January 29, 2019: Developmental and Comparative Immunology
Simon A Lowe, Maria M Usowicz, James J L Hodge
Down syndrome (DS) is characterised by abnormal cognitive and motor development, and later in life by progressive Alzheimer's disease (AD)-like dementia, neuropathology, declining motor function and shorter life expectancy. It is caused by trisomy of chromosome 21 (Hsa21), but how individual Hsa21 genes contribute to various aspects of the disorder is incompletely understood. Previous work has demonstrated a role for triplication of the Hsa21 gene DYRK1A in cognitive and motor deficits, as well as in altered neurogenesis and neurofibrillary degeneration in the DS brain, but its contribution to other DS phenotypes is unclear...
January 28, 2019: Neurobiology of Disease
Jiehong Kong, Yajing Qiu, Yuan Li, Hongjian Zhang, Weipeng Wang
Multidrug resistance (MDR) is common in patients and has been linked to transforming growth factor-β1 (TGF-β1) and overexpression of drug efflux transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), although molecular mechanisms remain largely unknown. Here, we aimed to investigate the mechanisms underlying TGF-β1-induced MDR in hepatocellular carcinoma (HCC) cells. We found that TGF-β1 upregulated HOX transcript antisense RNA (HOTAIR) expression in HCC cells. When drosophila mothers against decapentaplegic 4 (SMAD4) was silenced, HOTAIR expression was accordingly reduced...
January 30, 2019: Biopharmaceutics & Drug Disposition
Jia-Yi Wei, Pei-Chi Chung, Sao-Yu Chu, Hung-Hsiang Yu
Diverse types of neurons must be specified in the developing brain to form the functional neural circuits that are necessary for the execution of daily tasks. Here, we describe the participation of Forkhead box class O (FOXO) in cell fate specification of a small subset of Drosophila ventral olfactory projection neurons (vPNs). Using the two-color labeling system, twin-spot MARCM, we determined the temporal birth order of each vPN type, and this characterization served as a foundation to investigate regulators of cell fate specification...
January 27, 2019: Journal of Neurogenetics
Soojin Hwang, Haemin Jeong, Eun Hee Hong, Hae Mi Joo, Kyoung Sang Cho, Seon Young Nam
Ionizing radiation is widely used in medicine and is valuable in both the diagnosis and treatment of many diseases. However, its health effects are ambiguous. Here, we report that low-dose ionizing radiation has beneficial effects in human amyloid-β42 (Aβ42)-expressing Drosophila Alzheimer's disease (AD) models. Ionizing radiation at a dose of 0.05 Gy suppressed AD-like phenotypes, including developmental defects and locomotive dysfunction, but did not alter the decreased survival rates and longevity of Aβ42-expressing flies...
January 22, 2019: Biology Open
Ipek Even, Sonja Reidenbach, Tanja Schlechter, Nicola Berns, Rosanna Herold, Wilfried Roth, Damir Krunic, Veit Riechmann, Ilse Hofmann
Cytoplasmic dynein-1 is a large minus-end-directed microtubule motor complex involved in membrane trafficking, organelle positioning and microtubule organization. The roles of dynein light intermediate chains (DLICs, DLIC1 and DLIC2) within the complex are however still largely undefined. In this study, we investigated the possible roles of DLICs in epithelial homeostasis and colon cancer development. Mutant clonal analysis of Drosophila Dlic in the follicular epithelium of Drosophila ovary showed defects in nuclear positioning, epithelial integrity and apical cell polarity...
January 18, 2019: FEBS Journal
Keunjung Heo, Su Min Lim, Minyeop Nahm, Young-Eun Kim, Ki-Wook Oh, Hwan Tae Park, Chang-Seok Ki, Seung Hyun Kim, Seungbok Lee
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that is frequently linked to microtubule abnormalities and mitochondrial trafficking defects. Whole exome sequencing (WES) of patient-parent trios has proven to be an efficient strategy for identifying rare de novo genetic variants responsible for sporadic ALS (sALS). Using a trio-WES approach, we identified a de novo RAPGEF2 variant (c.4069G>A, p.E1357K) in a patient with early-onset sALS. To assess the pathogenic effects of this variant, we have used patient-derived skin fibroblasts and motor neuron-specific overexpression of the RAPGEF2-E1357K mutant protein in Drosophila ...
December 2018: Experimental Neurobiology
Susanna Valanne, Tiina S Salminen, Mirva Järvelä-Stölting, Laura Vesala, Mika Rämet
Non-coding RNAs have important roles in regulating physiology, including immunity. Here, we performed transcriptome profiling of immune-responsive genes in Drosophila melanogaster during a Gram-positive bacterial infection, concentrating on long non-coding RNA (lncRNA) genes. The gene most highly induced by a Micrococcus luteus infection was CR44404, named Induced by Infection (lincRNA-IBIN). lincRNA-IBIN is induced by both Gram-positive and Gram-negative bacteria in Drosophila adults and parasitoid wasp Leptopilina boulardi in Drosophila larvae, as well as by the activation of the Toll or the Imd pathway in unchallenged flies...
January 11, 2019: PLoS Pathogens
Jonathan N Rosen, Mafalda Azevedo, David B Soffar, Vitaly P Boyko, Matthew B Brendel, Victoria K Schulman, Mary K Baylies
Skeletal muscle consists of multinucleated cells in which the myonuclei are evenly spaced throughout the cell. In Drosophila , this pattern is established in embryonic myotubes, where myonuclei move via microtubules (MTs) and the MT-associated protein Ensconsin (Ens)/MAP7, to achieve their distribution. Ens regulates multiple aspects of MT biology, but little is known about how Ens itself is regulated. We find that Ens physically interacts and colocalizes with Bsg25D, the Drosophila homologue of the centrosomal protein Ninein...
January 9, 2019: Journal of Cell Biology
Thomas K Smylla, Markus Meier, Anette Preiss, Dieter Maier
During development of higher animals, the Notch signalling pathway governs cell type specification by mediating appropriate gene expression responses. In the absence of signalling, Notch target genes are silenced by repressor complexes. In the model organism Drosophila melanogaster, the repressor complex includes the transcription factor Suppressor of Hairless [Su(H)] and Hairless (H) plus general co-repressors. Recent crystal structure analysis of the Drosophila Notch repressor revealed details of the Su(H)-H complex...
January 5, 2019: Development Genes and Evolution
Chiara Merigliano, Elisa Mascolo, Anthony Cesta, Isabella Saggio, Fiammetta Vernì
Aurora-A is a conserved mitotic kinase overexpressed in many types of cancer. Growing evidence shows that Aurora-A plays a crucial role in DNA damage response (DDR) although this aspect has been less characterized. We isolated a new aur-A mutation, named aur-A949 , in Drosophila, and we showed that it causes chromosome aberrations (CABs). In addition, aur-A949 mutants were sensitive to X-ray treatment and showed impaired γ-H2Av foci dissolution kinetics. To identify the pathway in which Aur-A works, we conducted an epistasis analysis by evaluating CAB frequencies in double mutants carrying aur-A949 mutation combined to mutations in genes related to DNA damage response (DDR)...
January 5, 2019: Chromosoma
Mahmoudreza Ramin, Yueyang Li, Wen-Tzu Chang, Hunter Shaw, Yong Rao
Natural aggressiveness is commonly observed in all animal species, and is displayed frequently when animals compete for food, territory and mating. Aggression is an innate behaviour, and is influenced by both environmental and genetic factors. However, the genetics of aggression remains largely unclear. In this study, we identify the peacefulness (pfs) gene as a novel player in the control of male-male aggression in Drosophila. Mutations in pfs decreased intermale aggressiveness, but did not affect locomotor activity, olfactory avoidance response and sexual behaviours...
January 3, 2019: Molecular Brain
Sven Reinhardt, Florian Schuck, Nicolai Stoye, Tobias Hartmann, Marcus O W Grimm, Gert Pflugfelder, Kristina Endres
BACKGROUND: The ADAM10-mediated cleavage of transmembrane proteins regulates cellular processes such as proliferation or migration. Substrate cleavage by ADAM10 has also been implicated in pathological situations such as cancer or Morbus Alzheimer. Therefore, identifying endogenous molecules, which modulate the amount and consequently the activity of ADAM10, might contribute to a deeper understanding of the enzyme's role in both, physiology and pathology. METHOD: To elucidate the underlying cellular mechanism of the TBX2-mediated repression of ADAM10 gene expression, we performed overexpression, RNAi-mediated knockdown and pharmacological inhibition studies in the human neuroblastoma cell line SH-SY5Y...
January 1, 2019: Cellular and Molecular Life Sciences: CMLS
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