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https://www.readbyqxmd.com/read/29051265/regulation-of-notch-signaling-by-rab7-and-rab8-requires-carboxyl-methylation-by-icmt
#1
Helen Court, Ian M Ahearn, Marc Amoyel, Erika A Bach, Mark R Philips
Isoprenylcysteine carboxyl methyltransferase (ICMT) methylesterifies C-terminal prenylcysteine residues of CaaX proteins and some RAB GTPases. Deficiency of either ICMT or NOTCH1 accelerates pancreatic neoplasia in Pdx1-Cre;LSL-Kras(G12D) mice, suggesting that ICMT is required for NOTCH signaling. We used Drosophila melanogaster wing vein and scutellar bristle development to screen Rab proteins predicted to be substrates for ICMT (ste14 in flies). We identified Rab7 and Rab8 as ICMT substrates that when silenced phenocopy ste14 deficiency...
October 19, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29046480/epigenetic-mechanisms-underlying-maternal-diabetes-associated-risk-of-congenital-heart-disease
#2
Madhumita Basu, Jun-Yi Zhu, Stephanie LaHaye, Uddalak Majumdar, Kai Jiao, Zhe Han, Vidu Garg
Birth defects are the leading cause of infant mortality, and they are caused by a combination of genetic and environmental factors. Environmental risk factors may contribute to birth defects in genetically susceptible infants by altering critical molecular pathways during embryogenesis, but experimental evidence for gene-environment interactions is limited. Fetal hyperglycemia associated with maternal diabetes results in a 5-fold increased risk of congenital heart disease (CHD), but the molecular basis for this correlation is unknown...
October 19, 2017: JCI Insight
https://www.readbyqxmd.com/read/29036187/analysis-of-transient-hypermorphic-activity-of-e-spl-d-during-r8-specification
#3
Adam T Majot, Ashok P Bidwai
Drosophila atonal (ato) is required for the specification of founding R8 photoreceptors during retinal development. ato is regulated via dual eye-specific enhancers; ato-3' is subject to initial induction whereas 5'-ato facilitates Notch-mediated autoregulation. Notch is further utilized to induce bHLH repressors of the E(spl) locus to restrict Ato from its initial broad expression to individual cells. Although Notch operates in two, distinct phases, it has remained unclear how the two phases maintain independence from one another...
2017: PloS One
https://www.readbyqxmd.com/read/29031909/the-retromer-subunit-vps26-mediates-notch-signaling-during-drosophila-oogenesis
#4
Rebecca Starble, Nancy J Pokrywka
During endocytosis, molecules are internalized by the cell through the invagination of the plasma membrane. Endocytosis is required for proper cell function and for normal development in Drosophila. One component of the endocytic pathway is the retromer complex, which recycles transmembrane proteins to other parts of the cell such as the plasma membrane and the trans-Golgi network. Previous studies have shown that mutations to the retromer complex result in developmental defects in Drosophila. In humans, retromer dysfunction has been implicated in Alzheimer's and Parkinson's disease, but little is known about the role of the retromer complex in Drosophila oogenesis...
October 11, 2017: Mechanisms of Development
https://www.readbyqxmd.com/read/29030483/rbpj-cbf1-interacts-with-l3mbtl3-mbt1-to-promote-repression-of-notch-signaling-via-histone-demethylase-kdm1a-lsd1
#5
Tao Xu, Sung-Soo Park, Benedetto Daniele Giaimo, Daniel Hall, Francesca Ferrante, Diana M Ho, Kazuya Hori, Lucas Anhezini, Iris Ertl, Marek Bartkuhn, Honglai Zhang, Eléna Milon, Kimberly Ha, Kevin P Conlon, Rork Kuick, Brandon Govindarajoo, Yang Zhang, Yuqing Sun, Yali Dou, Venkatesha Basrur, Kojo Sj Elenitoba-Johnson, Alexey I Nesvizhskii, Julian Ceron, Cheng-Yu Lee, Tilman Borggrefe, Rhett A Kovall, Jean-François Rual
Notch signaling is an evolutionarily conserved signal transduction pathway that is essential for metazoan development. Upon ligand binding, the Notch intracellular domain (NOTCH ICD) translocates into the nucleus and forms a complex with the transcription factor RBPJ (also known as CBF1 or CSL) to activate expression of Notch target genes. In the absence of a Notch signal, RBPJ acts as a transcriptional repressor. Using a proteomic approach, we identified L3MBTL3 (also known as MBT1) as a novel RBPJ interactor...
October 13, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29023471/combinatorial-action-of-grainyhead-extradenticle-and-notch-in-regulating-hox-mediated-apoptosis-in-drosophila-larval-cns
#6
Risha Khandelwal, Rashmi Sipani, Sriivatsan Govinda Rajan, Raviranjan Kumar, Rohit Joshi
Hox mediated neuroblast apoptosis is a prevalent way to pattern larval central nervous system (CNS) by different Hox genes, but the mechanism of this apoptosis is not understood. Our studies with Abdominal-A (Abd-A) mediated larval neuroblast (pNB) apoptosis suggests that AbdA, its cofactor Extradenticle (Exd), a helix-loop-helix transcription factor Grainyhead (Grh), and Notch signaling transcriptionally contribute to expression of RHG family of apoptotic genes. We find that Grh, AbdA, and Exd function together at multiple motifs on the apoptotic enhancer...
October 12, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28950873/modeling-and-analysis-of-the-delta-notch-dependent-boundary-formation-in-the-drosophila-large-intestine
#7
Fei Liu, Deshun Sun, Ryutaro Murakami, Hiroshi Matsuno
BACKGROUND: The boundary formation in the Drosophila large intestine is widely studied as an important biological problem. It has been shown that the Delta-Notch signaling pathway plays an essential role in the formation of boundary cells. RESULTS: In this paper, we propose a mathematical model for the Delta-Notch dependent boundary formation in the Drosophila large intestine in order to better interpret related experimental findings of this biological phenomenon...
September 21, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28928428/phosphorylation-of-suppressor-of-hairless-impedes-its-dna-binding-activity
#8
Anja C Nagel, Jasmin S Auer, Adriana Schulz, Jens Pfannstiel, Zhenyu Yuan, Courtney E Collins, Rhett A Kovall, Anette Preiss
Notch signalling activity governs cellular differentiation in higher metazoa, where Notch signals are transduced by the transcription factor CSL, called Suppressor of Hairless [Su(H)] in Drosophila. Su(H) operates as molecular switch on Notch target genes: within activator complexes, including intracellular Notch, or within repressor complexes, including the antagonist Hairless. Mass spectrometry identified phosphorylation on Serine 269 in Su(H), potentially serving as a point of cross-regulation by other signalling pathways...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28919436/the-notch-pathway-regulates-the-second-mitotic-wave-cell-cycle-independently-of-bhlh-proteins
#9
Abhishek Bhattacharya, Ke Li, Manon Quiquand, Gerard Rimesso, Nicholas E Baker
Notch regulates both neurogenesis and cell cycle activity to coordinate precursor cell generation in the differentiating Drosophila eye. Mosaic analysis with mitotic clones mutant for Notch components was used to identify the pathway of Notch signaling that regulates the cell cycle in the Second Mitotic Wave. Although S phase entry depends on Notch signaling and on the transcription factor Su(H), the transcriptional co-activator Mam and the bHLH repressor genes of the E(spl)-Complex were not essential, although these are Su(H) coactivators and targets during the regulation of neurogenesis...
September 14, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28861687/conservation-of-the-notch-antagonist-hairless-in-arthropods-functional-analysis-of-the-crustacean-daphnia-pulex-hairless-gene
#10
Ariella Zehender, Melanie Bayer, Milena Bauer, Bettina Zeis, Anette Preiss, Dieter Maier
The Notch signaling pathway is highly conserved in all animal metazoa: upon Notch receptor activation, transcription of Notch target genes is turned on by an activator complex that centers on the transcription factor CSL. In the absence of signal, CSL assembles transcriptional repression complexes that display remarkable evolutionary diversity. The major antagonist of Notch signaling in insects named Hairless was originally identified in Drosophila melanogaster. It binds to the Drosophila CSL homologue Suppressor of Hairless [Su(H)] and recruits the two general co-repressors, Groucho and C-terminal binding protein...
August 31, 2017: Development Genes and Evolution
https://www.readbyqxmd.com/read/28834743/constitutive-immune-activity-promotes-tumorigenesis-in-drosophila-intestinal-progenitor%C3%A2-cells
#11
Kristina Petkau, Meghan Ferguson, Silvia Guntermann, Edan Foley
Gut innate immune defenses control bacterial populations and protect the host interior from invasion. Although excess intestinal immune activity frequently promotes inflammatory illnesses, we know little about the consequences of chronic innate immune activity exclusively in endodermal gut cells of an otherwise normal animal. To address this question, we examined the consequences of persistent inflammatory signals in adult fly intestinal progenitor cells. We found that constitutive immune activity disrupts expression of homeostatic regulators such as Notch pathway components and induces hyperplasia throughout the gut...
August 22, 2017: Cell Reports
https://www.readbyqxmd.com/read/28794168/notch-signaling-in-development-tissue-homeostasis-and-disease
#12
REVIEW
Chris Siebel, Urban Lendahl
Notch signaling is an evolutionarily highly conserved signaling mechanism, but in contrast to signaling pathways such as Wnt, Sonic Hedgehog, and BMP/TGF-β, Notch signaling occurs via cell-cell communication, where transmembrane ligands on one cell activate transmembrane receptors on a juxtaposed cell. Originally discovered through mutations in Drosophila more than 100 yr ago, and with the first Notch gene cloned more than 30 yr ago, we are still gaining new insights into the broad effects of Notch signaling in organisms across the metazoan spectrum and its requirement for normal development of most organs in the body...
October 1, 2017: Physiological Reviews
https://www.readbyqxmd.com/read/28793250/mir-7-buffers-differentiation-in-the-developing-drosophila-visual-system
#13
Elizabeth E Caygill, Andrea H Brand
The 40,000 neurons of the medulla, the largest visual processing center of the Drosophila brain, derive from a sheet of neuroepithelial cells. During larval development, a wave of differentiation sweeps across the neuroepithelium, converting neuroepithelial cells into neuroblasts that sequentially express transcription factors specifying different neuronal cell fates. The switch from neuroepithelial cells to neuroblasts is controlled by a complex gene regulatory network and is marked by the expression of the proneural gene l'sc...
August 8, 2017: Cell Reports
https://www.readbyqxmd.com/read/28791751/the-gene-network-underlying-the-glial-regenerative-response-to-central-nervous-system-injury
#14
REVIEW
Kentaro Kato, Maria Losada-Perez, Alicia Hidalgo
Although the central nervous system does not regenerate, injury induces repair and regenerative responses in glial cells. In mammals, activated microglia clear up apoptotic cells and debris resulting from the injury, astrocytes form a scar that contains the lesion, and NG2-glia elicit a prominent regenerative response. NG2-glia regenerate themselves and differentiate into oligodendrocytes, which remyelinate axons leading to some recovery of locomotion. The regenerative response of glial cells is evolutionarily conserved across the animals and Drosophila genetics revealed an underlying gene network...
August 9, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28760393/sculpting-epithelia-with-planar-polarized-actomyosin-networks-principles-from-drosophila
#15
REVIEW
Tony J C Harris
Drosophila research has revealed how planar polarized actomyosin networks affect various types of tissue morphogenesis. The networks are positioned by both tissue-wide patterning factors (including Even-skipped, Runt, Engrailed, Invected, Hedgehog, Notch, Wingless, Epidermal Growth Factor, Jun N-terminal kinase, Sex combs reduced and Fork head) and local receptor complexes (including Echinoid, Crumbs and Toll receptors). Networks with differing super-structure and contractile output have been discovered. Their contractility can affect individual cells or can be coordinated across groups of cells, and such contractility can drive or resist physical change...
July 28, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28742844/control-of-runx-induced-repression-of-notch-signaling-by-mlf-and-its-partner-dnaj-1-during-drosophila-hematopoiesis
#16
Marion Miller, Aichun Chen, Vanessa Gobert, Benoit Augé, Mathilde Beau, Odile Burlet-Schiltz, Marc Haenlin, Lucas Waltzer
A tight regulation of transcription factor activity is critical for proper development. For instance, modifications of RUNX transcription factors dosage are associated with several diseases, including hematopoietic malignancies. In Drosophila, Myeloid Leukemia Factor (MLF) has been shown to control blood cell development by stabilizing the RUNX transcription factor Lozenge (Lz). However, the mechanism of action of this conserved family of proteins involved in leukemia remains largely unknown. Here we further characterized MLF's mode of action in Drosophila blood cells using proteomic, transcriptomic and genetic approaches...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28736165/intra-lineage-fate-decisions-involve-activation-of-notch-receptors-basal-to-the-midbody-in-drosophila-sensory-organ-precursor-cells
#17
Mateusz Trylinski, Khalil Mazouni, François Schweisguth
Notch receptors regulate cell fate decisions during embryogenesis and throughout adult life. In many cell lineages, binary fate decisions are mediated by directional Notch signaling between the two sister cells produced by cell division. How Notch signaling is restricted to sister cells after division to regulate intra-lineage decision is poorly understood. More generally, where ligand-dependent activation of Notch occurs at the cell surface is not known, as methods to detect receptor activation in vivo are lacking...
August 7, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28708823/notch-dependent-epithelial-fold-determines-boundary-formation-between-developmental-fields-in-the-drosophila-antenna
#18
Hui-Yu Ku, Y Henry Sun
Compartment boundary formation plays an important role in development by separating adjacent developmental fields. Drosophila imaginal discs have proven valuable for studying the mechanisms of boundary formation. We studied the boundary separating the proximal A1 segment and the distal segments, defined respectively by Lim1 and Dll expression in the eye-antenna disc. Sharp segregation of the Lim1 and Dll expression domains precedes activation of Notch at the Dll/Lim1 interface. By repressing bantam miRNA and elevating the actin regulator Enable, Notch signaling then induces actomyosin-dependent apical constriction and epithelial fold...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28662029/a-genetic-framework-controlling-the-differentiation-of-intestinal-stem-cells-during-regeneration-in-drosophila
#19
Zongzhao Zhai, Jean-Philippe Boquete, Bruno Lemaitre
The speed of stem cell differentiation has to be properly coupled with self-renewal, both under basal conditions for tissue maintenance and during regeneration for tissue repair. Using the Drosophila midgut model, we analyze at the cellular and molecular levels the differentiation program required for robust regeneration. We observe that the intestinal stem cell (ISC) and its differentiating daughter, the enteroblast (EB), form extended cell-cell contacts in regenerating intestines. The contact between progenitors is stabilized by cell adhesion molecules, and can be dynamically remodeled to elicit optimal juxtacrine Notch signaling to determine the speed of progenitor differentiation...
June 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28656157/opportunities-lost-and-gained-changes-in-progenitor-competence-during-nervous-system-development
#20
REVIEW
Dylan R Farnsworth, Chris Q Doe
During development of the central nervous system, a small pool of stem cells and progenitors generate the vast neural diversity required for neural circuit formation and behavior. Neural stem and progenitor cells often generate different progeny in response to the same signaling cue (e.g. Notch or Hedgehog), including no response at all. How does stem cell competence to respond to signaling cues change over time? Recently, epigenetics particularly chromatin remodeling - has emerged as a powerful mechanism to control stem cell competence...
2017: Neurogenesis (Austin, Tex.)
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