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https://www.readbyqxmd.com/read/29095923/pofut1-point-mutations-that-disrupt-o-fucosyltransferase-activity-destabilize-the-protein-and-abolish-notch1-signaling-during-mouse-somitogenesis
#1
Rieko Ajima, Emiko Suzuki, Yumiko Saga
The segmental pattern of the vertebrate body is established via the periodic formation of somites from the presomitic mesoderm (PSM). This periodical process is controlled by the cyclic and synchronized activation of Notch signaling in the PSM. Protein O-fucosyltransferase1 (Pofut1), which transfers O-fucose to the EGF domains of the Notch1 receptor, is indispensable for Notch signaling activation. The Drosophila homologue Ofut1 was reported to control Notch localization via two different mechanisms, working as a chaperone for Notch or as a regulator of Notch endocytosis...
2017: PloS One
https://www.readbyqxmd.com/read/28860380/glia-relay-differentiation-cues-to-coordinate-neuronal-development-in-drosophila
#2
Vilaiwan M Fernandes, Zhenqing Chen, Anthony M Rossi, Jaqueline Zipfel, Claude Desplan
Neuronal birth and specification must be coordinated across the developing brain to generate the neurons that constitute neural circuits. We used the Drosophila visual system to investigate how development is coordinated to establish retinotopy, a feature of all visual systems. Photoreceptors achieve retinotopy by inducing their target field in the optic lobe, the lamina neurons, with a secreted differentiation cue, epidermal growth factor (EGF). We find that communication between photoreceptors and lamina cells requires a signaling relay through glia...
September 1, 2017: Science
https://www.readbyqxmd.com/read/28847000/feedback-regulation-of-steady-state-epithelial-turnover-and-organ-size
#3
Jackson Liang, Shruthi Balachandra, Sang Ngo, Lucy Erin O'Brien
Epithelial organs undergo steady-state turnover throughout adult life, with old cells being continually replaced by the progeny of stem cell divisions. To avoid hyperplasia or atrophy, organ turnover demands strict equilibration of cell production and loss. However, the mechanistic basis of this equilibrium is unknown. Here we show that robustly precise turnover of the adult Drosophila intestine arises through a coupling mechanism in which enterocyte apoptosis breaks feedback inhibition of stem cell division...
August 31, 2017: Nature
https://www.readbyqxmd.com/read/28715417/a-hox-complex-activates-and-potentiates-the-epidermal-growth-factor-signaling-pathway-to-specify-drosophila-oenocytes
#4
Guolun Wang, Lisa Gutzwiller, David Li-Kroeger, Brian Gebelein
Hox transcription factors specify distinct cell types along the anterior-posterior axis of metazoans by regulating target genes that modulate signaling pathways. A well-established example is the induction of Epidermal Growth Factor (EGF) signaling by an Abdominal-A (Abd-A) Hox complex during the specification of Drosophila hepatocyte-like cells (oenocytes). Previous studies revealed that Abd-A is non-cell autonomously required to promote oenocyte fate by directly activating a gene (rhomboid) that triggers EGF secretion from sensory organ precursor (SOP) cells...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28535370/epithelial-patterning-morphogenesis-and-evolution-drosophila-eggshell-as-a-model
#5
REVIEW
Miriam Osterfield, Celeste A Berg, Stanislav Y Shvartsman
Understanding the mechanisms driving tissue and organ formation requires knowledge across scales. How do signaling pathways specify distinct tissue types? How does the patterning system control morphogenesis? How do these processes evolve? The Drosophila egg chamber, where EGF and BMP signaling intersect to specify unique cell types that construct epithelial tubes for specialized eggshell structures, has provided a tractable system to ask these questions. Work there has elucidated connections between scales of development, including across evolutionary scales, and fostered the development of quantitative modeling tools...
May 22, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28526325/expression-of-megf10-in-cholinergic-and-glutamatergic-neurons
#6
Yu Fujita, Tomoji Maeda, Koji Kamaishi, Rui Saito, Koyo Chiba, Xuefeng Shen, Kun Zou, Hiroto Komano
Multiple-EGF like domains 10 (MEGF10) is the mammalian homologue of Draper, a Drosophila phagocytosis receptor that plays an important role in synapse elimination and cell type-specific recognition. However, the expression and function of MEGF10 in the brain remain to be elucidated. Therefore, we aimed to clarify the regions and types of neurons that express MEGF10 in the brain, and to determine whether cells expressing MEGF10 possess phagocytic abilities. Our results indicated that MEGF10 is expressed in cholinergic and glutamatergic neurons of the cortex, hippocampus, and substantia nigra...
July 13, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28488382/neuron-specific-knockdown-of-the-drosophila-fat-induces-reduction-of-life-span-deficient-locomotive-ability-shortening-of-motoneuron-terminal-branches-and-defects-in-axonal-targeting
#7
Aya Nakamura, Ryo Tanaka, Kazushige Morishita, Hideki Yoshida, Yujiro Higuchi, Hiroshi Takashima, Masamitsu Yamaguchi
Mutations in FAT4 gene, one of the human FAT family genes, have been identified in Van Maldergem syndrome (VMS) and Hennekam lymphangiectasia-lymphedema syndrome (HS). The FAT4 gene encodes a large protein with extracellular cadherin repeats, EGF-like domains and Laminin G-like domains. FAT4 plays a role in tumor suppression and planar cell polarity. Drosophila contains a human FAT4 homologue, fat. Drosophila fat has been mainly studied with Drosophila eye and wing systems. Here, we specially knocked down Drosophila fat in nerve system...
May 9, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28485389/egfr-dependent-tor-independent-endocycles-support-drosophila-gut-epithelial-regeneration
#8
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/28428262/uncoupling-neurogenic-gene-networks-in-the-drosophila-embryo
#9
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/28408480/eogt-and-o-glcnac-on-secreted-and-membrane-proteins
#10
REVIEW
Shweta Varshney, Pamela Stanley
Here, we describe a recently discovered O-GlcNAc transferase termed EOGT for EGF domain-specific O-GlcNAc transferase. EOGT transfers GlcNAc (N-acetylglucosamine) to Ser or Thr in secreted and membrane proteins that contain one or more epidermal growth factor-like repeats with a specific consensus sequence. Thus, EOGT is distinct from OGT, the O-GlcNAc transferase, that transfers GlcNAc to Ser/Thr in proteins of the cytoplasm or nucleus. EOGT and OGT are in separate cellular compartments and have mostly distinct substrates, although both can act on cytoplasmic (OGT) and lumenal (EOGT) domains of transmembrane proteins...
April 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28202468/the-crumbs_c-isoform-of-drosophila-shows-tissue-and-stage-specific-expression-and-prevents-light-dependent-retinal-degeneration
#11
Stephanie Spannl, Alexandra Kumichel, Sarita Hebbar, Katja Kapp, Marcos Gonzalez-Gaitan, Sylke Winkler, Rosana Blawid, Gregor Jessberger, Elisabeth Knust
Drosophila Crumbs (Crb) is a key regulator of epithelial polarity and fulfils a plethora of other functions, such as growth regulation, morphogenesis of photoreceptor cells and prevention of retinal degeneration. This raises the question how a single gene regulates such diverse functions, which in mammals are controlled by three different paralogs. Here, we show that in Drosophila different Crb protein isoforms are differentially expressed as a result of alternative splicing. All isoforms are transmembrane proteins that differ by just one EGF-like repeat in their extracellular portion...
February 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28196077/enhancer-of-polycomb-coordinates-multiple-signaling-pathways-to-promote-both-cyst-and-germline-stem-cell-differentiation-in-the-drosophila-adult-testis
#12
Lijuan Feng, Zhen Shi, Xin Chen
Stem cells reside in a particular microenvironment known as a niche. The interaction between extrinsic cues originating from the niche and intrinsic factors in stem cells determines their identity and activity. Maintenance of stem cell identity and stem cell self-renewal are known to be controlled by chromatin factors. Herein, we use the Drosophila adult testis which has two adult stem cell lineages, the germline stem cell (GSC) lineage and the cyst stem cell (CySC) lineage, to study how chromatin factors regulate stem cell differentiation...
February 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28178204/epidermal-growth-factor-pathway-signaling-in-drosophila-embryogenesis-tools-for-understanding-cancer
#13
REVIEW
Jay B Lusk, Vanessa Y M Lam, Nicholas S Tolwinski
EGF signaling is a well-known oncogenic pathway in animals. It is also a key developmental pathway regulating terminal and dorsal-ventral patterning along with many other aspects of embryogenesis. In this review, we focus on the diverse roles for the EGF pathway in Drosophila embryogenesis. We review the existing body of evidence concerning EGF signaling in Drosophila embryogenesis focusing on current uncertainties in the field and areas for future study. This review provides a foundation for utilizing the Drosophila model system for research into EGF effects on cancer...
February 7, 2017: Cancers
https://www.readbyqxmd.com/read/27588814/evolution-of-new-cis-regulatory-motifs-required-for-cell-specific-gene-expression-in-caenorhabditis
#14
Michalis Barkoulas, Amhed M Vargas Velazquez, Alexandre E Peluffo, Marie-Anne FĂ©lix
Patterning of C. elegans vulval cell fates relies on inductive signaling. In this induction event, a single cell, the gonadal anchor cell, secretes LIN-3/EGF and induces three out of six competent precursor cells to acquire a vulval fate. We previously showed that this developmental system is robust to a four-fold variation in lin-3/EGF genetic dose. Here using single-molecule FISH, we find that the mean level of expression of lin-3 in the anchor cell is remarkably conserved. No change in lin-3 expression level could be detected among C...
September 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27535937/notch-mediated-lateral-inhibition-regulates-proneural-wave-propagation-when-combined-with-egf-mediated-reaction-diffusion
#15
Makoto Sato, Tetsuo Yasugi, Yoshiaki Minami, Takashi Miura, Masaharu Nagayama
Notch-mediated lateral inhibition regulates binary cell fate choice, resulting in salt and pepper patterns during various developmental processes. However, how Notch signaling behaves in combination with other signaling systems remains elusive. The wave of differentiation in the Drosophila visual center or "proneural wave" accompanies Notch activity that is propagated without the formation of a salt and pepper pattern, implying that Notch does not form a feedback loop of lateral inhibition during this process...
August 30, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27460034/modelling-with-animo-between-fuzzy-logic-and-differential-equations
#16
Stefano Schivo, Jetse Scholma, Paul E van der Vet, Marcel Karperien, Janine N Post, Jaco van de Pol, Rom Langerak
BACKGROUND: Computational support is essential in order to reason on the dynamics of biological systems. We have developed the software tool ANIMO (Analysis of Networks with Interactive MOdeling) to provide such computational support and allow insight into the complex networks of signaling events occurring in living cells. ANIMO makes use of timed automata as an underlying model, thereby enabling analysis techniques from computer science like model checking. Biology experts are able to use ANIMO via a user interface specifically tailored for biological applications...
July 27, 2016: BMC Systems Biology
https://www.readbyqxmd.com/read/27428513/structural-analysis-of-notch-regulating-rumi-reveals-basis-for-pathogenic-mutations
#17
Hongjun Yu, Hideyuki Takeuchi, Megumi Takeuchi, Qun Liu, Joshua Kantharia, Robert S Haltiwanger, Huilin Li
Rumi O-glucosylates the EGF repeats of a growing list of proteins essential in metazoan development, including Notch. Rumi is essential for Notch signaling, and Rumi dysregulation is linked to several human diseases. Despite Rumi's critical roles, it is unknown how Rumi glucosylates a serine of many but not all EGF repeats. Here we report crystal structures of Drosophila Rumi as binary and ternary complexes with a folded EGF repeat and/or donor substrates. These structures provide insights into the catalytic mechanism and show that Rumi recognizes structural signatures of the EGF motif, the U-shaped consensus sequence, C-X-S-X-(P/A)-C and a conserved hydrophobic region...
September 2016: Nature Chemical Biology
https://www.readbyqxmd.com/read/27379389/regulation-of-the-bmp-signaling-responsive-transcriptional-network-in-the-drosophila-embryo
#18
Lisa Deignan, Marco T Pinheiro, Catherine Sutcliffe, Abbie Saunders, Scott G Wilcockson, Leo A H Zeef, Ian J Donaldson, Hilary L Ashe
The BMP signaling pathway has a conserved role in dorsal-ventral axis patterning during embryonic development. In Drosophila, graded BMP signaling is transduced by the Mad transcription factor and opposed by the Brinker repressor. In this study, using the Drosophila embryo as a model, we combine RNA-seq with Mad and Brinker ChIP-seq to decipher the BMP-responsive transcriptional network underpinning differentiation of the dorsal ectoderm during dorsal-ventral axis patterning. We identify multiple new BMP target genes, including positive and negative regulators of EGF signaling...
July 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27129198/dual-roles-of-o-glucose-glycans-redundant-with-monosaccharide-o-fucose-on-notch-in-notch-trafficking
#19
Kenjiroo Matsumoto, Tomonori Ayukawa, Akira Ishio, Takeshi Sasamura, Tomoko Yamakawa, Kenji Matsuno
Notch is a transmembrane receptor that mediates cell-cell interactions and controls various cell-fate specifications in metazoans. The extracellular domain of Notch contains multiple epidermal growth factor (EGF)-like repeats. At least five different glycans are found in distinct sites within these EGF-like repeats. The function of these individual glycans in Notch signaling has been investigated, primarily by disrupting their individual glycosyltransferases. However, we are just beginning to understand the potential functional interactions between these glycans...
June 24, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/26792023/the-novel-tumour-suppressor-madm-regulates-stem-cell-competition-in-the-drosophila-testis
#20
Shree Ram Singh, Ying Liu, Jiangsha Zhao, Xiankun Zeng, Steven X Hou
Stem cell competition has emerged as a mechanism for selecting fit stem cells/progenitors and controlling tumourigenesis. However, little is known about the underlying molecular mechanism. Here we identify Mlf1-adaptor molecule (Madm), a novel tumour suppressor that regulates the competition between germline stem cells (GSCs) and somatic cyst stem cells (CySCs) for niche occupancy. Madm knockdown results in overexpression of the EGF receptor ligand vein (vn), which further activates EGF receptor signalling and integrin expression non-cell autonomously in CySCs to promote their overproliferation and ability to outcompete GSCs for niche occupancy...
2016: Nature Communications
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