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https://www.readbyqxmd.com/read/28424321/the-drosophila-zo-1-protein-polychaetoid-suppresses-deltex-regulated-notch-activity-to-modulate-germline-stem-cell-niche-formation
#1
Hideyuki Shimizu, Marian B Wilkin, Simon A Woodcock, Alessandro Bonfini, Yvonne Hung, Sabine Mazaleyrat, Martin Baron
The developmental signalling protein Notch can be proteolytically activated following ligand-interaction at the cell surface, or can be activated independently of its ligands, following Deltex (Dx)-induced Notch endocytosis and trafficking to the lysosomal membrane. The means by which different pools of Notch are directed towards these alternative outcomes remains poorly understood. We found that the Drosophila ZO-1 protein Polychaetoid (Pyd) suppresses specifically the Dx-induced form of Notch activation both in vivo and in cell culture assays...
April 2017: Open Biology
https://www.readbyqxmd.com/read/28406397/evolutionary-changes-in-transcription-factor-coding-sequence-quantitatively-alter-sensory-organ-development-and-function
#2
Simon Weinberger, Matthew P Topping, Jiekun Yan, Annelies Claeys, Natalie De Geest, Duru Ozbay, Talah Hassan, Xiaoli He, Joerg T Albert, Bassem A Hassan, Ariane Ramaekers
'Toolkit' genes are highly conserved developmental regulators. While changes in their regulatory elements contribute to morphological evolution, the role of coding sequence (CDS) evolution remains unresolved. We used CDS-specific knock-ins of the proneural transcription factor Atonal homologs (ATHs) to address this question. Drosophila Atonal CDS was endogenously replaced with that of distant ATHs at key phylogenetic positions, non-ATH proneural genes, and the closest CDS to ancestral proneural genes. ATHs and the ancestral-like gene rescued sensory organ fate in atonal mutants, in contrast to non-ATHs...
April 13, 2017: ELife
https://www.readbyqxmd.com/read/28396507/regulation-of-notch-signaling-by-the-heterogeneous-nuclear-ribonucleoprotein-hrp48-and-deltex-in-drosophila-melanogaster
#3
Debdeep Dutta, Maimuna Sali Paul, Ankita Singh, Mousumi Mutsuddi, Ashim Mukherjee
Notch signaling is an evolutionarily conserved pathway that is found to be involved in a number of cellular events throughout development. The deployment of Notch signaling pathway in numerous cellular contexts is possible due to its regulation at multiple levels. In an effort to identify the novel components integrated into the molecular circuitry affecting Notch signaling, we carried out a protein-protein interaction screen based on the identification of cellular protein complexes using co-immunoprecipitation followed by mass-spectrometry...
April 10, 2017: Genetics
https://www.readbyqxmd.com/read/28394894/tissue-specific-enhancer-repression-through-molecular-integration-of-cell-signaling-inputs
#4
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 10, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28394891/xylosylation-of-the-notch-receptor-preserves-the-balance-between-its-activation-by-trans-delta-and-inhibition-by-cis-ligands-in-drosophila
#5
Tom V Lee, Ashutosh Pandey, Hamed Jafar-Nejad
The Drosophila glucoside xylosyltransferase Shams xylosylates Notch and inhibits Notch signaling in specific contexts including wing vein development. However, the molecular mechanisms underlying context-specificity of the shams phenotype is not known. Considering the role of Delta-Notch signaling in wing vein formation, we hypothesized that Shams might affect Delta-mediated Notch signaling in Drosophila. Using genetic interaction studies, we find that altering the gene dosage of Delta affects the wing vein and head bristle phenotypes caused by loss of Shams or by mutations in the Notch xylosylation sites...
April 10, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28386027/self-organized-notch-dynamics-generate-stereotyped-sensory-organ-patterns-in-drosophila
#6
Francis Corson, Lydie Couturier, Hervé Rouault, Khalil Mazouni, François Schweisguth
The emergence of spatial patterns in developing multicellular organisms relies on positional cues and cell-cell communication. Drosophila sensory organs have informed a paradigm where these operate in two distinct steps: prepattern factors drive localized proneural activity, then Notch-mediated lateral inhibition singles out neural precursors. Here we show that self-organization through Notch signaling also organizes the proneural stripes that resolve into rows of sensory bristles on the fly thorax. Patterning, initiated by a gradient of Delta ligand expression, progresses through inhibitory signaling between and within stripes...
April 6, 2017: Science
https://www.readbyqxmd.com/read/28355214/a-new-paramutation-like-example-at-the-delta-gene-of-drosophila
#7
Maria Capovilla, Alain Robichon, Minoo Rassoulzadegan
The hereditary transmission of a phenotype independent from DNA sequence implies epigenetic effects. Paramutation is a heritable epigenetic phenomenon observed in plants and animals. To investigate paramutation in Drosophila, we used the P{ry+t7.2 = PZ}Dl05151 P-element insertion in the Drosophila melanogaster genome that causes a dominant visible phenotype: the presence of characteristic extra-veins in the fly wings. This extra-vein phenotype presents variable expressivity and incomplete penetrance. The insert is a PZ element located 680 bp upstream from the ATG of the Delta (Dl) gene, encoding the Notch ligand involved in wing vein development, and acts as a null allele...
2017: PloS One
https://www.readbyqxmd.com/read/28350987/the-super-elongation-complex-drives-neural-stem-cell-fate-commitment
#8
Kun Liu, Dan Shen, Jingwen Shen, Shihong M Gao, Bo Li, Chouin Wong, Weidong Feng, Yan Song
Asymmetric stem cell division establishes an initial difference between a stem cell and its differentiating sibling, critical for maintaining homeostasis and preventing carcinogenesis. Yet the mechanisms that consolidate and lock in such initial fate bias remain obscure. Here, we use Drosophila neuroblasts to demonstrate that the super elongation complex (SEC) acts as an intrinsic amplifier to drive cell fate commitment. SEC is highly expressed in neuroblasts, where it promotes self-renewal by physically associating with Notch transcription activation complex and enhancing HES (hairy and E(spl)) transcription...
March 27, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28347816/evolutionary-conservation-of-notch-signaling-inhibition-by-tmem131l-overexpression
#9
Sébastien Szuplewski, Nesrine Maharzi, Elisabeth Nelson, Kutaiba Alhaj Hussen, Bernard Mignotte, Isabelle Guénal, Bruno Canque
Human KIAA0922/TMEM131L encodes a transmembrane protein, TMEM131L, that regulates the canonical Wnt/β-catenin signaling pathway by eliciting the lysosome-dependent degradation of phosphorylated LRP6 co-receptor. Here, we use a heterospecific Drosophila transgenic model to examine the potential evolutionary conservation of TMEM131L function. Analysis of TMEM131L transgenic flies shows that TMEM131L interference with the Wnt pathway results primarily from a Notch-dependent decrease in Wingless production. Consistently, lentivirus-mediated overexpression of TMEM131L in human CD34(+) hematopoietic progenitor cells leads to decreased susceptibility to Notch1 ligation and defective commitment toward the T lineage...
March 24, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28347671/deletion-of-numb-numblike-in-glutamatergic-neurons-leads-to-anxiety-like-behavior-in-mice
#10
Wenyu Qian, Yang Hong, Minyan Zhu, Liang Zhou, Hongchang Li, Huashun Li
Endocytic adaptor protein Numb is the first identified cell fate determinant in Drosophila melanogaster. It has been implicated in Notch signaling pathway and regulation of neural stem cells proliferation in the central nervous system. Numb is also expressed in postmitotic neurons, in vitro studies showed that Numb is involved in neuronal morphologic development, such as neurite growth, axonal growth and spine development. However, in vivo functions of Numb in the postmitotic neurons are largely unknown. Here we show that deletion of Numb/Numblike in glutamatergic neurons causes anxiety-like behavior in mouse...
March 24, 2017: Brain Research
https://www.readbyqxmd.com/read/28327288/atrophin-controls-developmental-signaling-pathways-via-interactions-with-trithorax-like
#11
Kelvin Yeung, Ann Boija, Edvin Karlsson, Per-Henrik Holmqvist, Yonit Tsatskis, Ilaria Nisoli, Damian B Yap, Alireza Lorzadeh, Michelle Moksa, Martin Hirst, Samuel Aparicio, Manolis Fanto, Per Stenberg, Mattias Mannervik, Helen McNeill
Mutations in human Atrophin1, a transcriptional corepressor, cause dentatorubral-pallidoluysian atrophy, a neurodegenerative disease. Drosophila Atrophin (Atro) mutants display many phenotypes, including neurodegeneration, segmentation, patterning and planar polarity defects. Despite Atro's critical role in development and disease, relatively little is known about Atro's binding partners and downstream targets. We present the first genomic analysis of Atro using ChIP-seq against endogenous Atro. ChIP-seq identified 1300 potential direct targets of Atro including engrailed, and components of the Dpp and Notch signaling pathways...
March 22, 2017: ELife
https://www.readbyqxmd.com/read/28325554/inscuteable-maintains-type-i-neuroblast-lineage-identity-via-numb-notch-signaling-in-the-drosophila-larval-brain
#12
Huanping An, Wanzhong Ge, Yongmei Xi, Xiaohang Yang
In the Drosophila larval brain, type I and type II neuroblasts (NBs) undergo a series of asymmetric divisions which give rise to distinct progeny lineages. The intermediate neural progenitors (INPs) exist only in type II NB lineages. In this study, we reveal a novel function of Inscuteable (Insc) that acts to maintain type I NB lineage identity. In insc type I NB clones of mosaic analyses with a repressible cell marker (MARCM), the formation of extra Deadpan (Dpn)(+) NB-like and GMC-like cells is observed. The lack of Insc leads to the defective localization and segregation of Numb during asymmetric cell division...
March 6, 2017: Journal of Genetics and Genomics, Yi Chuan Xue Bao
https://www.readbyqxmd.com/read/28258114/dynamic-notch-signaling-specifies-each-cell-fate-in-drosophila-spermathecal-lineage
#13
Wei Shen, Jianjun Sun
Spermathecae are glandular organs in insect female reproductive tract and play essential roles for insect reproduction; however, the molecular mechanism involved in their development is largely unknown. Drosophila spermathecae consist of class-III secretory units, in which each secretory cell discharges its products to the central lumen through an end-apparatus and a canal. Secretory unit formation in Drosophila spermathecae utilizes a fixed cell lineage, in which each secretory unit precursor (SUP) divides to produce one pIIb cell and one pIIa cell...
March 3, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28257663/molecular-pathways-related-to-the-longevity-promotion-and-cognitive-improvement-of-cistanche-tubulosa-in-drosophila
#14
Wei-Yong Lin, Chun Yao, Jack Cheng, Shung-Te Kao, Fuu-Jen Tsai, Hsin-Ping Liu
BACKGROUND: The aging process, including physical dysfunction and age-related memory impairment (AMI), are considered to be correlated with cumulative oxidative damages and insulin/IGF-1 signaling pathway. PURPOSE: The present study was to elucidate the in vivo effects on delaying aging and ameliorating AMI and underlying molecular mechanisms of Cistanche tubulosa (CT), a herb used in traditional Chinese medicine to improve sexual function and treat kidney dysfunction...
March 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28250735/glial-kon-ng2-gene-network-for-central-nervous-system-repair
#15
REVIEW
Maria Losada-Perez, Neale Harrison, Alicia Hidalgo
The glial regenerative response to central nervous system (CNS) injury, although limited, can be harnessed to promote regeneration and repair. Injury provokes the proliferation of ensheathing glial cells, which can differentiate to remyelinate axons, and partially restore function. This response is evolutionarily conserved, strongly implying an underlying genetic mechanism. In mammals, it is elicited by NG2 glia, but most often newly generated cells fail to differentiate. Thus an important goal had been to find out how to promote glial differentiation following the proliferative response...
January 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28246214/the-e3-ubiquitin-ligase-nedd4-nedd4l-is-directly-regulated-by-microrna-1
#16
Jun-Yi Zhu, Amy Heidersbach, Irfan S Kathiriya, Bayardo I Garay, Kathryn N Ivey, Deepak Srivastava, Zhe Han, Isabelle N King
miR-1 is a small noncoding RNA molecule that modulates gene expression in heart and skeletal muscle. Loss of Drosophila miR-1 produces defects in somatic muscle and embryonic heart development, which have been partly attributed to miR-1 directly targeting Delta to decrease Notch signaling. Here, we show that overexpression of miR-1 in the fly wing can paradoxically increase Notch activity independently of its effects on Delta. Analyses of potential miR-1 targets revealed that miR-1 directly regulates the 3'UTR of the E3 ubiquitin ligase Nedd4 Analysis of embryonic and adult fly heart revealed that the Nedd4 protein regulates heart development in Drosophila Larval fly hearts overexpressing miR-1 have profound defects in actin filament organization that are partially rescued by concurrent overexpression of Nedd4...
March 1, 2017: Development
https://www.readbyqxmd.com/read/28242614/function-of-nerfin-1-in-preventing-medulla-neurons-dedifferentiation-requires-its-inhibition-of-notch-activity
#17
Jiajun Xu, Xue Hao, Meng-Xin Yin, Yi Lu, Yunyun Jin, Jinjin Xu, Ling Ge, Wenqing Wu, Margaret Ho, Yingzi Yang, Yun Zhao, Lei Zhang
Drosophila larval central nervous system comprises the central brain, ventral nerve cord and optic lobe. In these regions, neuroblasts divide asymmetrically to self-renew and generate differentiated neurons or glia. To date, mechanisms of preventing neuron dedifferentiation is still unclear, especially in the optic lobe. Here we show that the zinc finger transcription factor Nerfin-1 is expressed in early stage of medulla neurons and essential for maintaining their differentiation. Loss of Nerfin-1 activates Notch signaling, which promotes neuron-to-NB reversion...
February 27, 2017: Development
https://www.readbyqxmd.com/read/28218276/natural-and-laboratory-mutations-in-kuzbanian-are-associated-with-zinc-stress-phenotypes-in-drosophila-melanogaster
#18
Hung Le Manh, Lain Guio, Miriam Merenciano, Quirze Rovira, Maite G Barrón, Josefa González
Organisms must cope with altered environmental conditions such as high concentrations of heavy metals. Stress response to heavy metals is mediated by the metal-responsive transcription factor 1 (MTF-1), which is conserved from Drosophila to humans. MTF-1 binds to metal response elements (MREs) and changes the expression of target genes. kuzbanian (kuz), a metalloendopeptidase that activates the evolutionary conserved Notch signaling pathway, has been identified as an MTF-1 target gene. We have previously identified a putatively adaptive transposable element in the Drosophila melanogaster genome, named FBti0019170, inserted in a kuz intron...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28174242/diversity-of-fate-outcomes-in-cell-pairs-under-lateral-inhibition
#19
Nara Guisoni, Rosa Martinez-Corral, Jordi Garcia Ojalvo, Joaquín de Navascués
Cell fate determination by lateral inhibition via Notch/Delta signalling has been extensively studied. Most formalised models consider Notch/Delta interactions in fields of cells, with parameters that typically lead to symmetry breaking of signalling states between neighbouring cells, commonly resulting in salt-and-pepper fate patterns. Here we consider the case of signalling between isolated cell pairs, and find that the bifurcation properties of a standard mathematical model of lateral inhibition can lead to stable symmetric signalling states...
February 7, 2017: Development
https://www.readbyqxmd.com/read/28174239/ataxin-2-binding-protein-1-is-a-context-specific-positive-regulator-of-notch-signaling-during-neurogenesis-in-drosophila-melanogaster
#20
Jay Prakash Shukla, Girish Deshpande, L S Shashidhara
The role of the Notch pathway during the lateral inhibition that underlies binary cell fate choice is extensively studied, but the context specificity that generates diverse outcomes is less well understood. In the peripheral nervous system of Drosophila melanogaster, differential Notch signaling between cells of the proneural cluster orchestrates sensory organ specification. Here we report functional analysis of Drosophila Ataxin 2-binding protein 1 (A2BP1) during this process. Its human ortholog is linked to type 2 spinocerebellar ataxia and other complex neuronal disorders...
March 1, 2017: Development
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