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Drosophila egfr

Mariana Fregoso Lomas, Scott De Vito, Jean-François Boisclair Lachance, Josée Houde, Laura A Nilson
A relatively small number of signaling pathways drive a wide range of developmental decisions, but how this versatility in signaling outcome is generated is not clear. In the Drosophila follicular epithelium, localized epidermal growth factor receptor (EGFR) activation induces distinct cell fates depending on its location. Posterior follicle cells respond to EGFR activity by expressing the T-box transcription factors Midline and H15, while anterior cells respond by expressing the homeodomain transcription factor Mirror...
October 10, 2016: Current Biology: CB
Anubha Mahajan, Aylin R Rodan, Thu H Le, Kyle J Gaulton, Jeffrey Haessler, Adrienne M Stilp, Yoichiro Kamatani, Gu Zhu, Tamar Sofer, Sanjana Puri, Jeffrey N Schellinger, Pei-Lun Chu, Sylvia Cechova, Natalie van Zuydam, Johan Arnlov, Michael F Flessner, Vilmantas Giedraitis, Andrew C Heath, Michiaki Kubo, Anders Larsson, Cecilia M Lindgren, Pamela A F Madden, Grant W Montgomery, George J Papanicolaou, Alex P Reiner, Johan Sundström, Timothy A Thornton, Lars Lind, Erik Ingelsson, Jianwen Cai, Nicholas G Martin, Charles Kooperberg, Koichi Matsuda, John B Whitfield, Yukinori Okada, Cathy C Laurie, Andrew P Morris, Nora Franceschini
We analyzed genome-wide association studies (GWASs), including data from 71,638 individuals from four ancestries, for estimated glomerular filtration rate (eGFR), a measure of kidney function used to define chronic kidney disease (CKD). We identified 20 loci attaining genome-wide-significant evidence of association (p < 5 × 10(-8)) with kidney function and highlighted that allelic effects on eGFR at lead SNPs are homogeneous across ancestries. We leveraged differences in the pattern of linkage disequilibrium between diverse populations to fine-map the 20 loci through construction of "credible sets" of variants driving eGFR association signals...
September 1, 2016: American Journal of Human Genetics
Mehrnoush Dehghani, Paul Lasko
The DEAD-box RNA helicase Vasa (Vas, also known as DDX4) is required for germ cell development. In Drosophila, analysis of hypomorphic mutations has implicated maternally expressed Vas in germ cell formation and posterior embryonic patterning. vas-null females, which rarely complete oogenesis, exhibit defects in mitotic progression of germline stem cells, Piwi-interacting RNA (piRNA)-mediated transposon silencing, and translation of Gurken (Grk), an EGFR ligand. The carboxy-terminal region of Vas orthologs throughout the animal kingdom consists of several acidic residues as well as an invariant tryptophan in the penultimate or ultimate position (Trp660 in Drosophila melanogaster)...
August 29, 2016: Development Genes and Evolution
Noemie Ammeux, Benjamin E Housden, Andrew Georgiadis, Yanhui Hu, Norbert Perrimon
During development and homeostasis, cells integrate multiple signals originating either from neighboring cells or systemically. In turn, responding cells can produce signals that act in an autocrine, paracrine, or endocrine manner. Although the nature of the signals and pathways used in cell-cell communication are well characterized, we lack, in most cases, an integrative view of signaling describing the spatial and temporal interactions between pathways (e.g., whether the signals are processed sequentially or concomitantly when two pathways are required for a specific outcome)...
August 30, 2016: Proceedings of the National Academy of Sciences of the United States of America
Mohna Bandyopadhyay, Clifton P Bishop, Ashok P Bidwai
The specification of patterned R8 photoreceptors at the onset of eye development depends on timely inhibition of Atonal (Ato) by the Enhancer of split (E(spl) repressors. Repression of Ato by E(spl)-M8 requires the kinase CK2 and is inhibited by the phosphatase PP2A. The region targeted by CK2 harbors additional conserved Ser residues, raising the prospect of regulation via multi-site phosphorylation. Here we investigate one such motif that meets the consensus for modification by MAPK, a well-known effector of Epidermal Growth Factor Receptor (EGFR) signaling...
2016: PloS One
Xiao-Xuan Xin, Yong Chen, Di Chen, Fa Xiao, Laurence D Parnell, Jing Zhao, Liang Liu, Jose M Ordovas, Chao-Qiang Lai, Li-Rong Shen
The major royal-jelly proteins (MRJPs) are the main constituents responsible for the specific physiological role of royal jelly (RJ) in honeybees. Male and female Drosophila flies were fed diets containing either no MRJPs (A) or casein (B) at 1.25% (w/w) of diet or MRJPs at 1.25% (C), 2.50% (D), or 5.00% (E). Diets B, C, D, and E increased mean lifespan by 4.3%, 9.0%, 12.4%, and 13.9% in males and by 5.8%, 9.7%, 20.0%, and 11.8% in females in comparison to results from diet A, respectively. The diet supplemented with 2...
July 27, 2016: Journal of Agricultural and Food Chemistry
Kouhei Shimaji, Takahiro Konishi, Hideki Yoshida, Hiroshi Kimura, Masamitsu Yamaguchi
G9a is one of the histone H3 Lys 9 (H3K9) specific methyltransferases first identified in mammals. Drosophila G9a (dG9a) has been reported to induce H3K9 dimethylation in vivo, and the target genes of dG9a were identified during embryonic and larval stages. Although dG9a is important for a variety of developmental processes, the link between dG9a and signaling pathways are not addressed yet. Here, by genome-wide genetic screen, taking advantage of the rough eye phenotype of flies that over-express dG9a in eye discs, we identified 16 genes that enhanced the rough eye phenotype induced by dG9a over-expression...
August 1, 2016: Experimental Cell Research
Huiming Yang, Mengjie Li, Xiaolong Hu, Tianchi Xin, Shu Zhang, Gengchun Zhao, Tao Xuan, Mingfa Li
The Drosophila larval ovary morphogenesis mainly involves coordinated development of somatic and germ cell lineages that is essential for forming a correct number of niche-germline stem cell (GSC) units (ovarioles) in the adult ovary. Ecdysone, Insulin, Activin, Dpp and EGFR signaling pathways form a regulatory network that orchestrates ovarian soma and germ line throughout larval development. Identification and characterization of additional genes or machineries involved in this process will provide more insights into the underlying mechanisms...
August 15, 2016: Developmental Biology
Lindsey R Klebanow, Emanuela C Peshel, Andrew T Schuster, Kuntal De, Kavitha Sarvepalli, Madeleine E Lemieux, Jessica J Lenoir, Adrian W Moore, Jocelyn A McDonald, Michelle S Longworth
The pattern of the Drosophila melanogaster adult wing is heavily influenced by the expression of proteins that dictate cell fate decisions between intervein and vein during development. dSRF (Blistered) expression in specific regions of the larval wing disc promotes intervein cell fate, whereas EGFR activity promotes vein cell fate. Here, we report that the chromatin-organizing protein CAP-D3 acts to dampen dSRF levels at the anterior/posterior boundary in the larval wing disc, promoting differentiation of cells into the anterior crossvein...
August 1, 2016: Development
Lina Wunderle, Julia D Knopf, Nathalie Kühnle, Aymeric Morlé, Beate Hehn, Colin Adrain, Kvido Strisovsky, Matthew Freeman, Marius K Lemberg
Rhomboid intramembrane proteases are the enzymes that release active epidermal growth factor receptor (EGFR) ligands in Drosophila and C. elegans, but little is known about their functions in mammals. Here we show that the mammalian rhomboid protease RHBDL4 (also known as Rhbdd1) promotes trafficking of several membrane proteins, including the EGFR ligand TGFα, from the endoplasmic reticulum (ER) to the Golgi apparatus, thereby triggering their secretion by extracellular microvesicles. Our data also demonstrate that RHBDL4-dependent trafficking control is regulated by G-protein coupled receptors, suggesting a role for this rhomboid protease in pathological conditions, including EGFR signaling...
2016: Scientific Reports
Li-Ping Chen, Pan Wang, Ying-Jian Sun, Yi-Jun Wu
With the widespread use of avermectins (AVMs) for managing parasitic and agricultural pests, the resistance of worms and insects to AVMs has emerged as a serious threat to human health and agriculture worldwide. The reduced penetration of AVMs is one of the main reasons for the development of the resistance to the chemicals. However, the detailed molecular mechanisms remain elusive. Here, we use the larvae of Drosophila melanogaster as the model organism to explore the molecular mechanisms underlying the development of penetration resistance to AVMs...
April 2016: Open Biology
Hao Zhu, Markus R Owen, Yanlan Mao
MOTIVATION: Animals from worms and insects to birds and mammals show distinct body plans; however, the embryonic development of diverse body plans with tissues and organs within is controlled by a surprisingly few signaling pathways. It is well recognized that combinatorial use of and dynamic interactions among signaling pathways follow specific logic to control complex and accurate developmental signaling and patterning, but it remains elusive what such logic is, or even, what it looks like...
August 1, 2016: Bioinformatics
Nicholas D Testa, Ian Dworkin
Much of the morphological diversity in nature-including among sexes within a species-is a direct consequence of variation in size and shape. However, disentangling variation in sexual dimorphism for both shape (SShD), size (SSD), and their relationship with one another remains complex. Understanding how genetic variation influences both size and shape together, and how this in turn influences SSD and SShD, is challenging. In this study, we utilize Drosophila wing size and shape as a model system to investigate how mutations influence size and shape as modulated by sex...
June 2016: Development Genes and Evolution
Anja C Nagel, Jutta Szawinski, Mirjam Zimmermann, Anette Preiss
Notch signalling regulates a multitude of differentiation processes during Drosophila development. For example, Notch activity is required for proper wing vein differentiation which is hampered in mutants of either the receptor Notch, the ligand Delta or the antagonist Hairless. Moreover, the Notch pathway is involved in several aspects of Drosophila oogenesis as well. We have identified Drosophila Cyclin G (CycG) as a molecular interaction partner of Hairless, the major antagonist in the Notch signalling pathway, in vitro and in vivo...
2016: PloS One
Marianne Malartre
EGFR signalling is a well-conserved signalling pathway playing major roles during development and cancers. This review explores what studying the EGFR pathway during Drosophila eye development has taught us in terms of the diversity of its regulatory mechanisms. This model system has allowed the identification of numerous positive and negative regulators acting at specific time and place, thus participating to the tight control of signalling. EGFR signalling regulation is achieved by a variety of mechanisms, including the control of ligand processing, the availability of the receptor itself and the transduction of the cascade in the cytoplasm...
May 2016: Cellular and Molecular Life Sciences: CMLS
Angela Zacher, Kerstin Kaulich, Stefanie Stepanow, Marietta Wolter, Karl Köhrer, Jörg Felsberg, Bastian Malzkorn, Guido Reifenberger
Current classification of gliomas is based on histological criteria according to the World Health Organization (WHO) classification of tumors of the central nervous system. Over the past years, characteristic genetic profiles have been identified in various glioma types. These can refine tumor diagnostics and provide important prognostic and predictive information. We report on the establishment and validation of gene panel next generation sequencing (NGS) in the molecular diagnostics of gliomas. We designed a glioma-tailored gene panel covering 660 amplicons derived from 20 genes frequently aberrant in different glioma types...
February 25, 2016: Brain Pathology
Min-Young Lee, Ki-Hoan Nam, Kyung-Chul Choi
In Drosophila, rhomboid proteases are active cardinal regulators of epidermal growth factor receptor (EGFR) signaling pathway. iRhom1 and iRhom2, which are inactive homologs of rhomboid intramembrane serine proteases, are lacking essential catalytic residues. These are necessary for maturation and traffickingof tumor necrosis factor-alpha (TNF-α) converting enzyme (TACE) from endoplasmic reticulum (ER) to plasma membrane through Golgi, and associated with the fates of various ligands for EGFR. Recent studies have clarifiedthat the activation or downregulation of EGFR signaling pathways by alteration of iRhoms are connected to several human diseases including tylosis with esophageal cancer (TOC) which is the autosomal dominant syndrom, breast cancer, and Alzheimer's disease...
March 1, 2016: Biomolecules & Therapeutics
Teresa Eichenlaub, Stephen M Cohen, Héctor Herranz
Cell competition is a homeostatic process in which proliferating cells compete for survival. Elimination of otherwise normal healthy cells through competition is important during development and has recently been shown to contribute to maintaining tissue health during organismal aging. The mechanisms that allow for ongoing cell competition during adult life could, in principle, contribute to tumorigenesis. However, direct evidence supporting this hypothesis has been lacking. Here, we provide evidence that cell competition drives tumor formation in a Drosophila model of epithelial cancer...
February 22, 2016: Current Biology: CB
Jasmin S Auer, Anja C Nagel, Adriana Schulz, Vanessa Wahl, Anette Preiss
In Drosophila, Notch and EGFR signalling pathways are closely intertwined. Their relationship is mostly antagonistic, and may in part be based on the phosphorylation of the Notch signal transducer Suppressor of Hairless [Su(H)] by MAPK. Su(H) is a transcription factor that together with several cofactors regulates the expression of Notch target genes. Here we address the consequences of a local induction of three Su(H) variants on Notch target gene expression. To this end, wild-type Su(H), a phospho-deficient Su(H) (MAPK-) (ko) and a phospho-mimetic Su(H) (MAPK-ac) isoform were overexpressed in the central domain of the wing anlagen...
December 2015: Data in Brief
Yinhua Jin, Nati Ha, Marta Forés, Jinyi Xiang, Christine Gläßer, Julieta Maldera, Gerardo Jiménez, Bruce A Edgar
Epithelial renewal in the Drosophila intestine is orchestrated by Intestinal Stem Cells (ISCs). Following damage or stress the intestinal epithelium produces ligands that activate the epidermal growth factor receptor (EGFR) in ISCs. This promotes their growth and division and, thereby, epithelial regeneration. Here we demonstrate that the HMG-box transcriptional repressor, Capicua (Cic), mediates these functions of EGFR signaling. Depleting Cic in ISCs activated them for division, whereas overexpressed Cic inhibited ISC proliferation and midgut regeneration...
December 2015: PLoS Genetics
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