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https://www.readbyqxmd.com/read/28485389/egfr-dependent-tor-independent-endocycles-support-drosophila-gut-epithelial-regeneration
#1
Jinyi Xiang, Jennifer Bandura, Peng Zhang, Yinhua Jin, Hanna Reuter, Bruce A Edgar
Following gut epithelial damage, epidermal growth factor receptor/mitogen-activated protein kinase (EGFR/MAPK) signalling triggers Drosophila intestinal stem cells to produce enteroblasts (EBs) and enterocytes (ECs) that regenerate the gut. As EBs differentiate into ECs, they become postmitotic, but undergo extensive growth and DNA endoreplication. Here we report that EGFR/RAS/MAPK signalling is required and sufficient to drive damage-induced EB/EC growth. Endoreplication occurs exclusively in EBs and newborn ECs that inherit EGFR and active MAPK from fast-dividing progenitors...
May 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28467418/a-kcnc3-mutation-causes-a-neurodevelopmental-non-progressive-sca13-subtype-associated-with-dominant-negative-effects-and-aberrant-egfr-trafficking
#2
Swati Khare, Jerelyn A Nick, Yalan Zhang, Kira Galeano, Brittany Butler, Habibeh Khoshbouei, Sruti Rayaprolu, Tyisha Hathorn, Laura P W Ranum, Lisa Smithson, Todd E Golde, Martin Paucar, Richard Morse, Michael Raff, Julie Simon, Magnus Nordenskjöld, Karin Wirdefeldt, Diego E Rincon-Limas, Jada Lewis, Leonard K Kaczmarek, Pedro Fernandez-Funez, Harry S Nick, Michael F Waters
The autosomal dominant spinocerebellar ataxias (SCAs) are a diverse group of neurological disorders anchored by the phenotypes of motor incoordination and cerebellar atrophy. Disease heterogeneity is appreciated through varying comorbidities: dysarthria, dysphagia, oculomotor and/or retinal abnormalities, motor neuron pathology, epilepsy, cognitive impairment, autonomic dysfunction, and psychiatric manifestations. Our study focuses on SCA13, which is caused by several allelic variants in the voltage-gated potassium channel KCNC3 (Kv3...
2017: PloS One
https://www.readbyqxmd.com/read/28444830/gene-expression-reveals-evidence-for-egfr-dependent-proximal-distal-limb-patterning-in-a-myriapod
#3
Ralf Janssen
Evolution of segmented limbs is one of the key innovations of Arthropoda, allowing development of functionally specific specialized head and trunk appendages, a major factor behind their unmatched evolutionary success. Proximodistal limb patterning is controlled by two regulatory networks in the vinegar fly Drosophila melanogaster, and other insects. The first is represented by the function of the morphogens Wingless (Wg) and Decapentaplegic (Dpp); the second by the EGFR-signaling cascade. While the role of Wg and Dpp has been studied in a wide range of arthropods representing all main branches, that is, Pancrustacea (= Hexapoda + Crustacea), Myriapoda and Chelicerata, investigation of the potential role of EGFR-signaling is restricted to insects (Hexapoda)...
April 26, 2017: Evolution & Development
https://www.readbyqxmd.com/read/28428262/uncoupling-neurogenic-gene-networks-in-the-drosophila-embryo
#4
William A Rogers, Yogesh Goyal, Kei Yamaya, Stanislav Y Shvartsman, Michael S Levine
The EGF signaling pathway specifies neuronal identities in the Drosophila embryo by regulating developmental patterning genes such as intermediate neuroblasts defective (ind). EGFR is activated in the ventral midline and neurogenic ectoderm by the Spitz ligand, which is processed by the Rhomboid protease. CRISPR/Cas9 was used to delete defined rhomboid enhancers mediating expression at each site of Spitz processing. Surprisingly, the neurogenic ectoderm, not the ventral midline, was found to be the dominant source of EGF patterning activity...
April 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28394894/tissue-specific-enhancer-repression-through-molecular-integration-of-cell-signaling-inputs
#5
Luis Humberto Mojica-Vázquez, Mikhail H Benetah, Aissette Baanannou, Sandra Bernat-Fabre, Bart Deplancke, David L Cribbs, Henri-Marc Bourbon, Muriel Boube
Drosophila leg morphogenesis occurs under the control of a relatively well-known genetic cascade, which mobilizes both cell signaling pathways and tissue-specific transcription factors. However, their cross-regulatory interactions, deployed to refine leg patterning, remain poorly characterized at the gene expression level. Within the genetically interacting landscape that governs limb development, the bric-à-brac2 (bab2) gene is required for distal leg segmentation. We have previously shown that the Distal-less (Dll) homeodomain and Rotund (Rn) zinc-finger activating transcription factors control limb-specific bab2 expression by binding directly a single critical leg/antennal enhancer (LAE) within the bric-à-brac locus...
April 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28363744/dref-plays-multiple-roles-during-drosophila-development
#6
REVIEW
Nguyen Trong Tue, Yasuhide Yoshioka, Megumi Mizoguchi, Hideki Yoshida, Mario Zurita, Masamitsu Yamaguchi
DREF was originally identified as a transcription factor that coordinately regulates the expression of DNA replication- and proliferation-related genes in Drosophila. Subsequent studies demonstrated that DREF is involved in tumor suppressor pathways including p53 and Hippo signaling. DREF also regulates the expression of genes encoding components of the JNK and EGFR pathways during Drosophila development. DREF itself is under the control of the TOR pathway during cell and tissue growth responding to nutrition...
June 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28281543/egfr-arf6-regulation-of-hh-signalling-stimulates-oncogenic-ras-tumour-overgrowth
#7
Chiswili Chabu, Da-Ming Li, Tian Xu
Multiple signalling events interact in cancer cells. Oncogenic Ras cooperates with Egfr, which cannot be explained by the canonical signalling paradigm. In turn, Egfr cooperates with Hedgehog signalling. How oncogenic Ras elicits and integrates Egfr and Hedgehog signals to drive overgrowth remains unclear. Using a Drosophila tumour model, we show that Egfr cooperates with oncogenic Ras via Arf6, which functions as a novel regulator of Hh signalling. Oncogenic Ras induces the expression of Egfr ligands. Egfr then signals through Arf6, which regulates Hh transport to promote Hh signalling...
March 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28092921/the-ligand-sas-and-its-receptor-ptp10d-drive-tumour-suppressive-cell-competition
#8
Masatoshi Yamamoto, Shizue Ohsawa, Kei Kunimasa, Tatsushi Igaki
Normal epithelial cells often exert anti-tumour effects against nearby oncogenic cells. In the Drosophila imaginal epithelium, clones of oncogenic cells with loss-of-function mutations in the apico-basal polarity genes scribble or discs large are actively eliminated by cell competition when surrounded by wild-type cells. Although c-Jun N-terminal kinase (JNK) signalling plays a crucial role in this cell elimination, the initial event, which occurs at the interface between normal cells and polarity-deficient cells, has not previously been identified...
February 9, 2017: Nature
https://www.readbyqxmd.com/read/27989519/the-function-of-appendage-patterning-genes-in-mandible-development-of-the-sexually-dimorphic-stag-beetle
#9
Hiroki Gotoh, Robert A Zinna, Yuki Ishikawa, Hitoshi Miyakawa, Asano Ishikawa, Yasuhiro Sugime, Douglas J Emlen, Laura C Lavine, Toru Miura
One of the defining features of the evolutionary success of insects is the morphological diversification of their appendages, especially mouthparts. Although most insects share a common mouthpart ground plan, there is remarkable diversity in the relative size and shapes of these appendages among different insect lineages. One of the most prominent examples of mouthpart modification can be found in the enlargement of mandibles in stag beetles (Coleoptera, Insecta). In order to understand the proximate mechanisms of mouthpart modification, we investigated the function of appendage-patterning genes in mandibular enlargement during extreme growth of the sexually dimorphic mandibles of the stag beetle Cyclommatus metallifer...
December 16, 2016: Developmental Biology
https://www.readbyqxmd.com/read/27974623/genetic-regulation-and-function-of-epidermal-growth-factor-receptor-signalling-in-patterning-of-the-embryonic-drosophila-brain
#10
David Jussen, Janina von Hilchen, Rolf Urbach
The specification of distinct neural cell types in central nervous system development crucially depends on positional cues conferred to neural stem cells in the neuroectoderm. Here, we investigate the regulation and function of the epidermal growth factor receptor (EGFR) signalling pathway in early development of the Drosophila brain. We find that localized EGFR signalling in the brain neuroectoderm relies on a neuromere-specific deployment of activating (Spitz, Vein) and inhibiting (Argos) ligands. Activated EGFR controls the spatially restricted expression of all dorsoventral (DV) patterning genes in a gene- and neuromere-specific manner...
December 2016: Open Biology
https://www.readbyqxmd.com/read/27888216/drosophila-sulf1-is-required-for-the-termination-of-intestinal-stem-cell-division-during-regeneration
#11
Masahiko Takemura, Hiroshi Nakato
Stem cell division is activated to trigger regeneration in response to tissue damage. The molecular mechanisms by which this stem cell mitotic activity is properly repressed at the end of regeneration are poorly understood. Here, we show that a specific modification of heparan sulfate is crucial for regulating Drosophila intestinal stem cell (ISC) division during normal midgut homeostasis and regeneration. Loss of the extracellular heparan sulfate endosulfatase Sulf1 resulted in increased ISC division during normal homeostasis, which was caused by upregulation of mitogenic signaling including the JAK-STAT, EGFR and Hedgehog pathways...
January 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/27836963/phosphorylated-groucho-delays-differentiation-in-the-follicle-stem-cell-lineage-by-providing-a-molecular-memory-of-egfr-signaling-in-the-niche
#12
Michael J Johnston, Shaked Bar-Cohen, Ze'ev Paroush, Todd G Nystul
In the epithelial follicle stem cells (FSCs) of the Drosophila ovary, Epidermal Growth Factor Receptor (EGFR) signaling promotes self-renewal, whereas Notch signaling promotes differentiation of the prefollicle cell (pFC) daughters. We have identified two proteins, Six4 and Groucho (Gro), that link the activity of these two pathways to regulate the earliest cell fate decision in the FSC lineage. Our data indicate that Six4 and Gro promote differentiation towards the polar cell fate by promoting Notch pathway activity...
December 15, 2016: Development
https://www.readbyqxmd.com/read/27835572/sprouty2-inhibits-amphiregulin-induced-down-regulation-of-e-cadherin-and-cell-invasion-in-human-ovarian-cancer-cells
#13
Jung-Chien Cheng, Hsun-Ming Chang, Siyuan Xiong, Wai-Kin So, Peter C K Leung
Similar to Drosophila Sprouty (SPRY), mammalian SPRY proteins inhibit the receptor tyrosine kinase-mediated activation of cellular signaling pathways. SPRY2 expression levels have been shown to be down-regulated in human ovarian cancer, and patients with low SPRY2 expression have significantly poorer survival than those with high SPRY2 expression. In addition, epidermal growth factor receptor (EGFR) is overexpressed in human ovarian cancer and is associated with more aggressive clinical behavior and a poor prognosis...
December 6, 2016: Oncotarget
https://www.readbyqxmd.com/read/27593379/determination-of-egfr-signaling-output-by-opposing-gradients-of-bmp-and-jak-stat-activity
#14
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
https://www.readbyqxmd.com/read/27588450/trans-ethnic-fine-mapping-highlights-kidney-function-genes-linked-to-salt-sensitivity
#15
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
https://www.readbyqxmd.com/read/27572922/c-terminal-residues-specific-to-vasa-among-dead-box-helicases-are-required-for-its-functions-in-pirna-biogenesis-and-embryonic-patterning
#16
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)...
November 2016: Development Genes and Evolution
https://www.readbyqxmd.com/read/27528688/mapping-signaling-pathway-cross-talk-in-drosophila-cells
#17
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
https://www.readbyqxmd.com/read/27428327/the-conserved-mapk-site-in-e-spl-m8-an-effector-of-drosophila-notch-signaling-controls-repressor-activity-during-eye-development
#18
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
https://www.readbyqxmd.com/read/27388939/supplementation-with-major-royal-jelly-proteins-increases-lifespan-feeding-and-fecundity-in-drosophila
#19
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
https://www.readbyqxmd.com/read/27343629/genome-wide-genetic-screen-identified-the-link-between-dg9a-and-epidermal-growth-factor-receptor-signaling-pathway-in-vivo
#20
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
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