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Drosophila egfr

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https://www.readbyqxmd.com/read/28791646/studying-nonproliferative-roles-for-egfr-signaling-in-tissue-morphogenesis-using-dorsal-closure-of-the-drosophila-embryo
#1
Bruce Reed, Nicholas Harden
For several decades, genetic analysis in Drosophila has made important contributions to the understanding of signaling by Egfr. Egfr has been well characterized with regard to its oncogenic potential but is also being studied for its roles in organismal development. We have recently developed dorsal closure of the Drosophila embryo as a system for characterizing Egfr regulation of events that do not involve proliferation, as no cell divisions occur during this process. Dorsal closure is essentially a developmental wound healing event with parallels to vertebrate developmental epithelial fusions such as neural tube closure and palate fusion...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28791632/new-insights-from-drosophila-into-the-regulation-of-egfr-signaling
#2
Nicholas Harden
Genetic analysis of Egfr signaling in Drosophila has a long-standing track record of making important contributions to our understanding of the Egfr pathway. While the central Ras/MAPK pathway has long been well defined, there is much to learn with regard to its cross talk with other pathways and how it is regulated. A better understanding of the regulation of Egfr signaling is of particular interest with regard to the participation of misregulated Egfr signaling in tumorigenesis. Recent studies in the fly have led to some surprising results, identifying regulators of Egfr acting in unexpected ways...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28754838/the-chromatin-remodeling-bap-complex-limits-tumor-promoting-activity-of-the-hippo-pathway-effector-yki-to-prevent-neoplastic-transformation-in-drosophila-epithelia
#3
Shilin Song, Héctor Herranz, Stephen M Cohen
SWI/SNF chromatin remodeling complexes are mutated in many human cancers. In this report we make use of a Drosophila genetic model for epithelial tumor formation to explore the tumor suppressive role of SWI/SNF complex proteins. Members of the BAP complex exhibit tumor suppressor activity in tissue overexpressing the Yorkie (Yki) proto-oncogene, but not in tissue overexpressing EGFR. The BAP complex has been reported to serve as a Yki-binding cofactor to support Yki target expression. However, we observed that depletion of BAP leads to ectopic expression of Yki targets both autonomously and non-autonomously, suggesting additional indirect effects...
July 28, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28701658/drosophila-dock-family-protein-zizimin-involves-in-pigment-cell-differentiation-in-pupal-retinae
#4
Fumito Ozasa, Kazushige Morishita, Ngoc Anh Suong Dang, Seiji Miyata, Hideki Yoshida, Masamitsu Yamaguchi
The dedicator of cytokinesis (DOCK) family proteins are known as one of guanine nucleotide exchange factors (GEFs), that contribute to cellular signaling processes by activating small G proteins. Although mammalian Zizimin is known to be a GEF for Cdc42 of Rho family small GTPase, its role in vivo is not well understood. Here we studied in vivo function of Drosophila Zizimin (Ziz). Knockdown of Ziz in eye imaginal discs induced the rough eye phenotype accompanied with fusion of ommatidia, loss of bristles and loss of pigments...
July 13, 2017: Cell Structure and Function
https://www.readbyqxmd.com/read/28678789/egfr-controls-drosophila-tracheal-tube-elongation-by-intracellular-trafficking-regulation
#5
Ivette Olivares-Castiñeira, Marta Llimargas
Development is governed by a few conserved signalling pathways. Amongst them, the EGFR pathway is used reiteratively for organ and tissue formation, and when dysregulated can lead to cancer and metastasis. Given its relevance, identifying its downstream molecular machinery and understanding how it instructs cellular changes is crucial. Here we approach this issue in the respiratory system of Drosophila. We identify a new role for EGFR restricting the elongation of the tracheal Dorsal Trunk. We find that EGFR regulates the apical determinant Crb and the extracellular matrix regulator Serp, two factors previously known to control tube length...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28676676/identifying-pathways-modulating-sleep-duration-from-genomics-to-transcriptomics
#6
Karla V Allebrandt, Maris Teder-Laving, Paola Cusumano, Goar Frishman, Rosa Levandovski, Andreas Ruepp, Maria P L Hidalgo, Rodolfo Costa, Andres Metspalu, Till Roenneberg, Cristiano De Pittà
Recognizing that insights into the modulation of sleep duration can emerge by exploring the functional relationships among genes, we used this strategy to explore the genome-wide association results for this trait. We detected two major signalling pathways (ion channels and the ERBB signalling family of tyrosine kinases) that could be replicated across independent GWA studies meta-analyses. To investigate the significance of these pathways for sleep modulation, we performed transcriptome analyses of short sleeping flies' heads (knockdown for the ABCC9 gene homolog; dSur)...
July 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28669604/redox-homeostasis-plays-important-roles-in-the-maintenance-of-the-drosophila-testis-germline-stem-cells
#7
Sharon Wui Sing Tan, Qian Ying Lee, Belinda Shu Ee Wong, Yu Cai, Gyeong Hun Baeg
Oxidative stress influences stem cell behavior by promoting the differentiation, proliferation, or apoptosis of stem cells. Thus, characterizing the effects of reactive oxygen species (ROS) on stem cell behavior provides insights into the significance of redox homeostasis in stem cell-associated diseases and efficient stem cell expansion for cellular therapies. We utilized the Drosophila testis as an in vivo model to examine the effects of ROS on germline stem cell (GSC) maintenance. High levels of ROS induced by alteration in Keap1/Nrf2 activity decreased GSC number by promoting precocious GSC differentiation...
July 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28628612/novel-interplay-between-jnk-and-egfr-signaling-in-drosophila-dorsal-closure
#8
Tatyana Kushnir, Sharon Mezuman, Shaked Bar-Cohen, Rotem Lange, Ze'ev Paroush, Aharon Helman
Dorsal closure (DC) is a developmental process in which two contralateral epithelial sheets migrate to seal a large hole in the dorsal ectoderm of the Drosophila embryo. Two signaling pathways act sequentially to orchestrate this dynamic morphogenetic process. First, c-Jun N-terminal kinase (JNK) signaling activity in the dorsal-most leading edge (LE) cells of the epidermis induces expression of decapentaplegic (dpp). Second, Dpp, a secreted TGF-β homolog, triggers cell shape changes in the adjacent, ventrally located lateral epidermis, that guide the morphogenetic movements and cell migration mandatory for DC...
June 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28621415/building-functional-units-of-movement-generation-and-movement-sensation-in-the-embryo
#9
Peleg Hasson, Talila Volk, Adi Salzberg
The musculoskeletal and proprioceptive sensory systems exhibit intricate crosstalk between force generation, force sensation and force transmission, all of which are critical for coordinated animal locomotion. Recent developmental studies of the musculoskeletal and proprioceptive units of the invertebrate Drosophila embryo, have revealed several common molecular and structural principles mediating the formation of each of these systems. These common principles, as well as the differences between the developmental programs of the two systems, are discussed...
2017: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/28619822/cop9-signalosome-subunits-protect-capicua-from-mapk-dependent-and-independent-mechanisms-of-degradation
#10
Annabelle Suisse, DanQing He, Kevin Legent, Jessica E Treisman
The COP9 signalosome removes Nedd8 modifications from the Cullin subunits of ubiquitin ligase complexes, reducing their activity. Here, we show that mutations in the Drosophila COP9 signalosome subunit 1b (CSN1b) gene increase the activity of ubiquitin ligases that contain Cullin 1. Analysis of CSN1b mutant phenotypes revealed a requirement for the COP9 signalosome to prevent ectopic expression of Epidermal growth factor receptor (EGFR) target genes. It does so by protecting Capicua, a transcriptional repressor of EGFR target genes, from EGFR pathway-dependent ubiquitylation by a Cullin 1/SKP1-related A/Archipelago E3 ligase and subsequent proteasomal degradation...
July 15, 2017: Development
https://www.readbyqxmd.com/read/28598558/conserved-signaling-mechanisms-in-drosophila-heart-development
#11
REVIEW
Shaad M Ahmad
Signal transduction through multiple distinct pathways regulates and orchestrates the numerous biological processes comprising heart development. This review outlines the roles of the FGFR, EGFR, Wnt, BMP, Notch, Hedgehog, Slit/Robo, and other signaling pathways during four sequential phases of Drosophila cardiogenesis-mesoderm migration, cardiac mesoderm establishment, differentiation of the cardiac mesoderm into distinct cardiac cell types, and morphogenesis of the heart and its lumen based on the proper positioning and cell shape changes of these differentiated cardiac cells-and illustrates how these same cardiogenic roles are conserved in vertebrates...
June 9, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28559239/escort-cells-generate-a-dynamic-compartment-for-germline-stem-cell-differentiation-via-combined-stat-and-erk-signalling
#12
Torsten U Banisch, Iris Maimon, Tali Dadosh, Lilach Gilboa
Two different compartments support germline stem cell (GSC) self-renewal and their timely differentiation: the classical niche provides maintenance cues, while a differentiation compartment, formed by somatic escort cells (ECs), is required for proper GSC differentiation. ECs extend long protrusions that invade between tightly packed germ cells, and alternate between encapsulating and releasing them. How ECs achieve this dynamic balance has not been resolved. By combining live imaging and genetic analyses in Drosophila, we have characterised EC shapes and their dynamic changes...
June 1, 2017: Development
https://www.readbyqxmd.com/read/28544778/differential-regulation-of-protein-tyrosine-kinase-signalling-by-dock-and-the-ptp61f-variants
#13
Lee F Willoughby, Jan Manent, Kirsten Allan, Han Lee, Marta Portela, Florian Wiede, Coral Warr, Tzu-Ching Meng, Tony Tiganis, Helena E Richardson
Tyrosine phosphorylation-dependent signalling is coordinated by the opposing actions of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). There is a growing list of adaptor proteins that interact with PTPs and facilitate the dephosphorylation of substrates. The extent to which any given adaptor confers selectivity for any given substrate in vivo remains unclear. Here we have taken advantage of Drosophila melanogaster as a model organism to explore the influence of the SH3/SH2 adaptor protein Dock on the abilities of the membrane (PTP61Fm)- and nuclear (PTP61Fn)-targeted variants of PTP61F (the Drosophila othologue of the mammalian enzymes PTP1B and TCPTP respectively) to repress PTK signalling pathways in vivo...
May 23, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28485389/egfr-dependent-tor-independent-endocycles-support-drosophila-gut-epithelial-regeneration
#14
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
#15
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
#16
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)...
May 2017: Evolution & Development
https://www.readbyqxmd.com/read/28428262/uncoupling-neurogenic-gene-networks-in-the-drosophila-embryo
#17
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
#18
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
#19
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
#20
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
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