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Drosophila egfe

Michalis Barkoulas, Amhed M Vargas Velazquez, Alexandre E Peluffo, Marie-Anne Félix
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
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
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...
2016: BMC Systems Biology
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
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
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
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
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
Josefa Cruz, Neus Bota-Rabassedas, Xavier Franch-Marro
How several signaling pathways are coordinated to generate complex organs through regulation of tissue growth and patterning is a fundamental question in developmental biology. The larval trachea of Drosophila is composed of differentiated functional cells and groups of imaginal tracheoblasts that build the adult trachea during metamorphosis. Air sac primordium cells (ASP) are tracheal imaginal cells that form the dorsal air sacs that supply oxygen to the flight muscles of the Drosophila adult. The ASP emerges from the tracheal branch that connects to the wing disc by the activation of both Bnl-FGF/Btl and EGFR signaling pathways...
2015: Scientific Reports
Olivier Biner, Christian Trachsel, Aline Moser, Lukas Kopp, Nicolas Langenegger, Urs Kämpfer, Christoph von Ballmoos, Wolfgang Nentwig, Stefan Schürch, Johann Schaller, Lucia Kuhn-Nentwig
STRUCTURE OF CUPIENNIUS SALEI VENOM HYALURONIDASE: Hyaluronidases are important venom components acting as spreading factor of toxic compounds. In several studies this spreading effect was tested on vertebrate tissue. However, data about the spreading activity on invertebrates, the main prey organisms of spiders, are lacking. Here, a hyaluronidase-like enzyme was isolated from the venom of the spider Cupiennius salei. The amino acid sequence of the enzyme was determined by cDNA analysis of the venom gland transcriptome and confirmed by protein analysis...
2015: PloS One
Nicolás Peláez, Arnau Gavalda-Miralles, Bao Wang, Heliodoro Tejedor Navarro, Herman Gudjonson, Ilaria Rebay, Aaron R Dinner, Aggelos K Katsaggelos, Luís A N Amaral, Richard W Carthew
Yan is an ETS-domain transcription factor responsible for maintaining Drosophila eye cells in a multipotent state. Yan is at the core of a regulatory network that determines the time and place in which cells transit from multipotency to one of several differentiated lineages. Using a fluorescent reporter for Yan expression, we observed a biphasic distribution of Yan in multipotent cells, with a rapid inductive phase and slow decay phase. Transitions to various differentiated states occurred over the course of this dynamic process, suggesting that Yan expression level does not strongly determine cell potential...
November 19, 2015: ELife
Masako Tamada, Jennifer A Zallen
Cells display dynamic and diverse morphologies during development, but the strategies by which differentiated tissues achieve precise shapes and patterns are not well understood. Here we identify a developmental program that generates a highly ordered square cell grid in the Drosophila embryo through sequential and spatially regulated cell alignment, oriented cell division, and apicobasal cell elongation. The basic leucine zipper transcriptional regulator Cnc is necessary and sufficient to produce a square cell grid in the presence of a midline signal provided by the EGF receptor ligand Spitz...
October 26, 2015: Developmental Cell
Jianchun Chen, Raymond C Harris
Activation of the EGF receptor (EGFR) or the Hippo signaling pathway can control cell proliferation, apoptosis, and differentiation, and the dysregulation of these pathways can contribute to tumorigenesis. Previous studies showed that activation of EGFR signaling in renal epithelial cells can exacerbate diabetic kidney injury. Moreover, EGFR has been implicated in regulating the Hippo signaling pathway in Drosophila; thus, we examined this potential interaction in mammalian diabetic kidney disease. Yes-associated protein (YAP) is a transcriptional regulator regulated by the Hippo signaling pathway...
June 2016: Journal of the American Society of Nephrology: JASN
Christopher M Smendziuk, Anat Messenberg, A Wayne Vogl, Guy Tanentzapf
Soma-germline interactions play conserved essential roles in regulating cell proliferation, differentiation, patterning and homeostasis in the gonad. In the Drosophila testis, secreted signalling molecules of the JAK-STAT, Hedgehog, BMP and EGF pathways are used to mediate soma-germline communication. Here, we demonstrate that gap junctions may also mediate direct, bi-directional signalling between the soma and germ line. When gap junctions between the soma and germ line are disrupted, germline differentiation is blocked and germline stem cells are not maintained...
August 1, 2015: Development
Linlin Yu, Qingxiang Zhou, Francesca Pignoni
The Gal4/UAS system is one of the most powerful tools for the study of cellular and developmental processes in Drosophila. Gal4 drivers can be used to induce targeted expression of dominant-negative and dominant-active proteins, histological markers, activity sensors, gene-specific dsRNAs, modulators of cell survival or proliferation, and other reagents. Here, we describe novel atonal-Gal4 lines that contain regions of the regulatory DNA of atonal, the proneural gene for photoreceptors, stretch receptors, auditory organ, and some olfactory sensilla...
June 2015: Genesis: the Journal of Genetics and Development
Maria-Dolores Martín-Bermudo, Pierre-Luc Bardet, Yohanns Bellaïche, Marianne Malartre
Organ shaping and patterning depends on the coordinated regulation of multiple processes. The Drosophila compound eye provides an excellent model to study the coordination of cell fate and cell positioning during morphogenesis. Here, we find that loss of vav oncogene function during eye development is associated with a disorganised retina characterised by the presence of additional cells of all types. We demonstrate that these defects result from two distinct roles of Vav. First, and in contrast to its well-established role as a positive effector of the EGF receptor (EGFR), we show that readouts of the EGFR pathway are upregulated in vav mutant larval eye disc and pupal retina, indicating that Vav antagonises EGFR signalling during eye development...
April 15, 2015: Development
Mitsutaka Ogawa, Shogo Sawaguchi, Koichi Furukawa, Tetsuya Okajima
BACKGROUND: O-linked β-N-acetylglucosamine (O-GlcNAc) modification of epidermal growth factor (EGF) domains catalyzed by EGF domain O-GlcNAc transferase (EOGT) is the first example of GlcNAc modification in the lumen of the endoplasmic reticulum (ER). SCOPE OF REVIEW: This review summarizes current knowledge on the EOGT-catalyzed O-GlcNAc modification of EGF domains obtained through biochemical characterization, genetic analysis in Drosophila, and identification of human EOGT mutation...
June 2015: Biochimica et Biophysica Acta
Till Matzat, Florian Sieglitz, Rita Kottmeier, Felix Babatz, Daniel Engelen, Christian Klämbt
Efficient neuronal conductance requires that axons are insulated by glial cells. For this, glial membranes need to wrap around axons. Invertebrates show a relatively simple extension of glial membranes around the axons, resembling Remak fibers formed by Schwann cells in the mammalian peripheral nervous system. To unravel the molecular pathways underlying differentiation of glial cells that provide axonal wrapping, we are using the genetically amenable Drosophila model. At the end of larval life, the wrapping glia differentiates into very large cells, spanning more than 1 mm of axonal length...
April 1, 2015: Development
Andrew J Bretscher, Viktor Honti, Olivier Binggeli, Olivier Burri, Mickael Poidevin, Éva Kurucz, János Zsámboki, István Andó, Bruno Lemaitre
Eater is an EGF-like repeat transmembrane receptor of the Nimrod family and is expressed in Drosophila hemocytes. Eater was initially identified for its role in phagocytosis of both Gram-positive and Gram-negative bacteria. We have deleted eater and show that it appears to be required for efficient phagocytosis of Gram-positive but not Gram-negative bacteria. However, the most striking phenotype of eater deficient larvae is the near absence of sessile hemocytes, both plasmatocyte and crystal cell types. The eater deletion is the first loss of function mutation identified that causes absence of the sessile hemocyte state...
2015: Biology Open
Weilin Wang, Rui Liu, Tao Zhang, Ran Zhang, Xuan Song, Lingling Wang, Linsheng Song
Phagocytosis is an evolutionarily conserved process to ingest the invading microbes and apoptotic or necrotic corpses, playing vital roles in defensing invaders and maintenance of normal physiological conditions. In the present study, a new Nimrod family phagocytic receptor with three EGF-like domains was identified in Pacific oyster Crassostrea gigas (designated CgNimC). CgNimC shared homology with other identified multiple EGF-like domain containing proteins. The mRNA transcripts of CgNimC were mainly distributed in mantle and hemocytes...
March 2015: Fish & Shellfish Immunology
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