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https://www.readbyqxmd.com/read/29210315/expression-of-lamina-proteins-lamin-and-kugelkern-suppresses-stem-cell-proliferation
#1
Roman Petrovsky, Jörg Großhans
The nuclear lamina is involved in numerous cellular functions, such as gene expression, nuclear organization, nuclear stability, and cell proliferation. The mechanism underlying the involvement of lamina is often not clear, especially in physiological or developmental contexts. Here we investigate the role and activity of farnesylated lamina proteins Lamin (Lam) and Kugelkern (Kuk) in proliferation control of intestinal stem cells (ISCs) in adult Drosophila flies. We found that ISCs mutant for Lam or kuk proliferate, whereas overexpression of Lam or Kuk strongly suppressed proliferation...
December 6, 2017: Nucleus
https://www.readbyqxmd.com/read/29208636/homeodomain-interacting-protein-kinase-promotes-tumorigenesis-and-metastatic-cell-behavior
#2
Jessica A Blaquiere, Kenneth Kin Lam Wong, Stephen D Kinsey, Jin Wu, Esther M Verheyen
Aberrations in signaling pathways that regulate tissue growth often lead to tumorigenesis. Homeodomain interacting protein kinase (Hipk) family members are reported to have distinct and contradictory effects on cell proliferation and tissue growth. From these studies it is clear that much remains to be learned about the roles of Hipk family protein kinases in proliferation and cell behaviour. Previous work has shown that Drosophila Hipk is a potent growth regulator, thus we predicted that it could have a role in tumorigenesis...
November 20, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29208631/the-drosophila-junctophilin-gene-is-functionally-equivalent-to-its-four-mammalian-counterparts-and-is-a-modifier-of-a-huntingtin-poly-q-expansion-and-the-notch-pathway
#3
Eduardo Calpena, Víctor López Del Amo, Mouli Chakraborty, Beatriz Llamusí, Rubén Artero, Carmen Espinós, Máximo I Galindo
Members of the Junctophilin (JPH) protein family have emerged as key actors in all excitable cells with critical implications for human pathophysiology. In mammals this family consists in four members (JPH1-4) that are differentially expressed throughout excitable cells. The analysis of knockout mice lacking JPH subtypes has demonstrated their essential contribution to physiological functions in skeletal and cardiac muscles, and neurons. Moreover, mutations in the human JPH2 gene are associated with hypertrophic and dilated cardiomyopathies; mutations in JPH3 are responsible for the neurodegenerative Huntington's disease-like-2 (HDL2), whereas JPH1 acts as a genetic modifier in CMT2K peripheral neuropathy...
November 20, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29205612/homeodomain-interacting-protein-kinase-phosphorylates-the-drosophila-paired-box-protein-6-pax6-homologues-twin-of-eyeless-and-eyeless
#4
E L Steinmetz, D N Dewald, U Walldorf
Homeodomain-interacting protein kinase (Hipk), the Drosophila homologue of mammalian HIPK2, plays several important roles in regulating differentiation, proliferation, apoptosis, and stress responses and acts as a mediator for signals of diverse pathways, such as Notch or Wingless signalling. The Paired box protein 6 (Pax6) has two Drosophila homologues, Twin of eyeless (Toy) and Eyeless (Ey). Both stand atop the retinal determination gene network (RDGN), which is essential for proper eye development in Drosophila...
December 4, 2017: Insect Molecular Biology
https://www.readbyqxmd.com/read/29196461/mirna-suppression-of-a-notch-repressor-directs-non-neuronal-fate-in-drosophila-mechanosensory-organs
#5
Joshua Kavaler, Hong Duan, Rajaguru Aradhya, Luis F de Navas, Brian Joseph, Boris Shklyar, Eric C Lai
Although there is abundant evidence that individual microRNA (miRNA) loci repress large cohorts of targets, large-scale knockout studies suggest that most miRNAs are phenotypically dispensable. Here, we identify a rare case of developmental cell specification that is highly dependent on miRNA control of an individual target. We observe that binary cell fate choice in the Drosophila melanogaster peripheral sensory organ lineage is controlled by the non-neuronally expressed mir-279/996 cluster, with a majority of notum sensory organs exhibiting transformation of sheath cells into ectopic neurons...
December 1, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29171103/adult-functions-for-the-drosophila-dhr78-nuclear-receptor
#6
Stefanie Marxreiter, Carl S Thummel
BACKGROUND: The Testicular Receptors 2 and 4 (TR2, TR4) comprise a small subfamily of orphan nuclear receptors. Genetic studies in mouse models have identified roles for TR4 in developmental progression, fertility, brain development, and metabolism, as well as genetic redundancy with TR2. Here we study the adult functions of the single Drosophila member of this subfamily, DHR78, with the goal of defining its ancestral functions in the absence of genetic redundancy. RESULTS: We show that DHR78 mutants have a shortened lifespan, reduced motility, and mated DHR78 mutant females display a reduced feeding rate...
November 24, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/29157562/erk-regulates-mitochondrial-membrane-potential-in-fission-deficient-drosophila-follicle-cells-during-differentiation
#7
Darshika Tomer, Rohan Chippalkatti, Kasturi Mitra, Richa Rikhy
Mitochondrial morphology regulatory proteins interact with signaling pathways involved in differentiation. In Drosophila oogenesis, EGFR signaling regulates mitochondrial fragmentation in posterior follicle cells (PFCs). EGFR driven oocyte patterning and Notch signaling mediated differentiation are abrogated when PFCs are deficient for the mitochondrial fission protein Drp1. It is not known whether fused mitochondrial morphology in drp1 mutant PFCs exerts its effects on these signaling pathways through change in mitochondrial electron transport chain (ETC) activity...
November 17, 2017: Developmental Biology
https://www.readbyqxmd.com/read/29155828/role-of-co-repressor-genomic-landscapes-in-shaping-the-notch-response
#8
Stephen K K Chan, Gustavo Cerda-Moya, Robert Stojnic, Kat Millen, Bettina Fischer, Silvie Fexova, Lenka Skalska, Maria Gomez-Lamarca, Zoe Pillidge, Steven Russell, Sarah J Bray
Repressors are frequently deployed to limit the transcriptional response to signalling pathways. For example, several co-repressors interact directly with the DNA-binding protein CSL and are proposed to keep target genes silenced in the absence of Notch activity. However, the scope of their contributions remains unclear. To investigate co-repressor activity in the context of this well defined signalling pathway, we have analysed the genome-wide binding profile of the best-characterized CSL co-repressor in Drosophila, Hairless, and of a second CSL interacting repressor, SMRTER...
November 20, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29155012/litopenaeus-vannamei-notch-affects-lipopolysaccharides-induced-reactive-oxygen-species
#9
Pei Ning, Zhihong Zheng, Jude Juventus Aweya, Defu Yao, Shengkang Li, Hongyu Ma, Fan Wang, Yueling Zhang
Notch signaling pathway was originally discovered in the development stage of drosophila but has recently been found to play essential roles in innate immunity. Most previous studies on Notch have focused on mammals, whereas, in this study, we employed the shrimp Litopenaeus vannamei as a model to study the functions of Notch in invertebrate innate immune system. Our results showed that LvNotch was highly expressed in hemocytes and could be strongly induced by lipopolysaccharides (LPS) injection. Small interfering RNA (siRNA)-mediated knockdown of LvNotch could significantly increase LPS induced L...
November 15, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29126016/go-and-stop-signals-for-glial-regeneration
#10
REVIEW
Alicia Hidalgo, Ann Logan
The regenerative response of ensheating glia to central nervous system (CNS) injury involves proliferation and differentiation, axonal re-enwrapment and some recovery of behaviour. Understanding this limited response could enable the enhancement of it. In Drosophila, the glial progenitor state is maintained by Notch, an activator of cell division and Prospero (Pros), a repressor. Injury provokes the activation of NFκB and up-regulation of Kon-tiki (Kon), driving cell proliferation. Homeostatic switch-off comes about as two negative feedback loops involving Pros terminate the response...
November 7, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/29108672/foxa-transcription-factor-fork-head-maintains-the-intestinal-stem-progenitor-cell-identities-in-drosophila
#11
Qing Lan, Min Cao, Rahul K Kollipara, Jeffrey B Rosa, Ralf Kittler, Huaqi Jiang
Understanding how somatic stem cells respond to tissue needs is important, since aberrant somatic stem cell behaviors may lead to tissue degeneration or tumorigenesis. Here, from an in vivo RNAi screen targeting transcription factors that regulate intestinal regeneration, we uncovered a requirement for the Drosophila FoxA transcription factor Fork head (Fkh) in the maintenance of intestinal stem/progenitor cell identities. FoxA/Fkh maintains the expressions of stem/progenitor cell markers and is required for stem cell proliferation during intestinal homeostasis and regeneration...
September 14, 2017: Developmental Biology
https://www.readbyqxmd.com/read/29102770/overexpression-of-djmj-differentially-affects-intestinal-stem-cells-and-differentiated-enterocytes
#12
Dang Ngoc Anh Suong, Kouhei Shimaji, Jung-Hoon Pyo, Joung-Sun Park, Hideki Yoshida, Mi-Ae Yoo, Masamitsu Yamaguchi
Jumonji (Jmj)/Jarid2 is a DNA-binding transcriptional repressor mediated via histone methylation. Nevertheless, the well-known function of Jmj is as a scaffold for the recruitment of various complexes including Polycomb repressive complex 2 (PRC2), and required for mouse embryonic stem cell development. However, PRC2 independent function is suggested for Drosophila Jumonji (dJmj). To clarify the function of dJmj during cell differentiation, we used Drosophila adult intestinal stem cell system that allows to follow stem cell behaviors in vivo...
November 2, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29095923/pofut1-point-mutations-that-disrupt-o-fucosyltransferase-activity-destabilize-the-protein-and-abolish-notch1-signaling-during-mouse-somitogenesis
#13
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/29093440/quantitative-microscopy-of-the-drosophila-ovary-shows-multiple-niche-signals-specify-progenitor-cell-fate
#14
Wei Dai, Amy Peterson, Thomas Kenney, Haley Burrous, Denise J Montell
Adult stem cells commonly give rise to transit-amplifying progenitors, whose progeny differentiate into distinct cell types. It is unclear if stem cell niche signals coordinate fate decisions within the progenitor pool. Here we use quantitative analysis of Wnt, Hh, and Notch signalling reporters and the cell fate markers Eyes Absent (Eya) and Castor (Cas) to study the effects of hyper-activation and loss of niche signals on progenitor development in the Drosophila ovary. Follicle stem cell (FSC) progeny adopt distinct polar, stalk, and main body cell fates...
November 1, 2017: Nature Communications
https://www.readbyqxmd.com/read/29072161/identification-and-functional-characterization-of-muscle-satellite-cells-in-drosophila
#15
Dhananjay Chaturvedi, Heinrich Reichert, Rajesh D Gunage, K VijayRaghavan
Work on genetic model systems such as Drosophila and mouse has shown that the fundamental mechanisms of myogenesis are remarkably similar in vertebrates and invertebrates. Strikingly, however, satellite cells, the adult muscle stem cells that are essential for the regeneration of damaged muscles in vertebrates, have not been reported in invertebrates. In this study, we show that lineal descendants of muscle stem cells are present in adult muscle of Drosophila as small, unfused cells observed at the surface and in close proximity to the mature muscle fibers...
October 26, 2017: ELife
https://www.readbyqxmd.com/read/29051265/regulation-of-notch-signaling-by-rab7-and-rab8-requires-carboxyl-methylation-by-icmt
#16
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
#17
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
#18
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
#19
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
#20
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...
November 2, 2017: EMBO Journal
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