110 results match your criteria mutations overproliferation


Structural variation at the maize WUSCHEL1 locus alters stem cell organization in inflorescences.

Nat Commun 2021 04 22;12(1):2378. Epub 2021 Apr 22.

Waksman Institute of Microbiology, Rutgers University, Piscataway, NJ, 08854-8020, USA.

Structural variation in plant genomes is a significant driver of phenotypic variability in traits important for the domestication and productivity of crop species. Among these are traits that depend on functional meristems, populations of stem cells maintained by the CLAVATA-WUSCHEL (CLV-WUS) negative feedback-loop that controls the expression of the WUS homeobox transcription factor. WUS function and impact on maize development and yield remain largely unexplored. Read More

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Multiple roles for Pax2 in the embryonic mouse eye.

Dev Biol 2021 Apr 9;472:18-29. Epub 2021 Jan 9.

Department of Cell Biology & Human Anatomy, University of California Davis, One Shields Avenue, Davis, CA, 95616, USA. Electronic address:

The vertebrate eye anlage grows out of the brain and folds into bilayered optic cups. The eye is patterned along multiple axes, precisely controlled by genetic programs, to delineate neural retina, pigment epithelium, and optic stalk tissues. Pax genes encode developmental regulators of key morphogenetic events, with Pax2 being essential for interpreting inductive signals, including in the eye. Read More

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Mitochondrial mutations and mitoepigenetics: Focus on regulation of oxidative stress-induced responses in breast cancers.

Semin Cancer Biol 2020 Oct 6. Epub 2020 Oct 6.

I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), 8/2 Trubetskaya Street, Moscow, 119991, Russia; Research Institute of Human Morphology, 3 Tsyurupy Street, Moscow, 117418, Russian Federation; Institute of Physiologically Active Compounds of Russian Academy of Sciences, Severny pr. 1, Chernogolovka, Moscow Region, 142432, Russia; GALLY International Research Institute, 7733 Louis Pasteur Drive, #330, San Antonio, TX, 78229, USA.

Epigenetic regulation of mitochondrial DNA (mtDNA) is an emerging and fast-developing field of research. Compared to regulation of nucler DNA, mechanisms of mtDNA epigenetic regulation (mitoepigenetics) remain less investigated. However, mitochondrial signaling directs various vital intracellular processes including aerobic respiration, apoptosis, cell proliferation and survival, nucleic acid synthesis, and oxidative stress. Read More

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October 2020

Transient Myeloproliferative Disorder: A Cytogenomic Update.

J Assoc Genet Technol 2020 ;46(2):74-91

The International Circle of Genetic Studies, Los Angeles, CA.

Objectives: Transient myeloproliferative disorder (TMD), now more commonly known as transient abnormal myelopoiesis (TAM), is a condition closely associated with Down syndrome. Ninety-five percent of Down syndrome cases occur as a result of chromosomal nondisjunction and are rarely due to mosaicism or translocation. TMD is found exclusively in neonates and is most commonly characterized by trisomy 21, somatic GATA1 mutation, and the increased presence of megakaryoblasts. Read More

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January 2020

Circadian regulation of mitochondrial uncoupling and lifespan.

Nat Commun 2020 04 21;11(1):1927. Epub 2020 Apr 21.

Department of Genetics and Development, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA.

Because old age is associated with defects in circadian rhythm, loss of circadian regulation is thought to be pathogenic and contribute to mortality. We show instead that loss of specific circadian clock components Period (Per) and Timeless (Tim) in male Drosophila significantly extends lifespan. This lifespan extension is not mediated by canonical diet-restriction longevity pathways but is due to altered cellular respiration via increased mitochondrial uncoupling. Read More

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Cerebral organoid and mouse models reveal a RAB39b-PI3K-mTOR pathway-dependent dysregulation of cortical development leading to macrocephaly/autism phenotypes.

Genes Dev 2020 04 27;34(7-8):580-597. Epub 2020 Feb 27.

Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, California 90033, USA.

Dysregulation of early neurodevelopment is implicated in macrocephaly/autism disorders. However, the mechanism underlying this dysregulation, particularly in human cells, remains poorly understood. Mutations in the small GTPase gene are associated with X-linked macrocephaly, autism spectrum disorder (ASD), and intellectual disability. Read More

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New insights into the early mechanisms of epileptogenesis in a zebrafish model of Dravet syndrome.

Epilepsia 2020 03 24;61(3):549-560. Epub 2020 Feb 24.

Chemical Neuroscience Group, Center for Molecular Medicine Norway, University of Oslo, Oslo, Norway.

Objective: To pinpoint the earliest cellular defects underlying seizure onset (epileptogenic period) during perinatal brain development in a new zebrafish model of Dravet syndrome (DS) and to investigate potential disease-modifying activity of the 5HT receptor agonist fenfluramine.

Methods: We used CRISPR/Cas9 mutagenesis to introduce a missense mutation, designed to perturb ion transport function in all channel isoforms, into scn1lab, the zebrafish orthologue of SCN1A (encoding voltage-gated sodium channel alpha subunit 1). We performed behavioral analysis and electroencephalographic recordings to measure convulsions and epileptiform discharges, followed by single-cell RNA-Seq, morphometric analysis of transgenic reporter-labeled γ-aminobutyric acidergic (GABAergic) neurons, and pharmacological profiling of mutant larvae. Read More

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WD40 protein Wuho controls germline homeostasis via TRIM-NHL tumor suppressor Mei-p26 in .

Development 2020 01 15;147(2). Epub 2020 Jan 15.

Molecular and Cell Biology, Taiwan International Graduate Program, Academia Sinica, Taipei 11529, Taiwan, R.O.C

WD40 proteins control many cellular processes via protein interactions. Wuho (Wh, a WD40 protein) controls fertility, although the involved mechanisms are unclear. Here, we show that Wh promotion of Mei-p26 (a human TRIM32 ortholog) function maintains ovarian germ cell homeostasis. Read More

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January 2020

E2FB Interacts with RETINOBLASTOMA RELATED and Regulates Cell Proliferation during Leaf Development.

Plant Physiol 2020 01 6;182(1):518-533. Epub 2019 Nov 6.

Institute of Plant Biology, Biological Research Centre, Szeged, 6726, Hungary

Cell cycle entry and quiescence are regulated by the E2F transcription factors in association with RETINOBLASTOMA-RELATED (RBR). E2FB is considered to be a transcriptional activator of cell cycle genes, but its function during development remains poorly understood. Here, by studying E2FB-RBR interaction, E2F target gene expression, and epidermal cell number and shape in mutant and overexpression lines during leaf development in Arabidopsis (), we show that E2FB in association with RBR plays a role in the inhibition of cell proliferation to establish quiescence. Read More

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January 2020

Transcriptional Corepressor ASP1 and CLV-Like Signaling Regulate Meristem Maintenance in Rice.

Plant Physiol 2019 07 11;180(3):1520-1534. Epub 2019 May 11.

Department of Biological Sciences, School of Science, The University of Tokyo, Bunkyo-ku, Tokyo 113-8654, Japan

Stem cell homeostasis is maintained by the WUSCHEL-CLAVATA (WUS-CLV) negative feedback loop in Arabidopsis (). In rice (), () functions in the negative regulation of stem cell proliferation, similar to Arabidopsis In this study, through genetic enhancer analysis, we found that loss of function of (), encoding an Arabidopsis TOPLESS (TPL)-like transcriptional corepressor, enhances the flower phenotype, which displayed an increase in floral organ number. In the double mutant, the inflorescence was severely affected, resulting in bifurcation of the main axis (rachis), a phenotype that has not previously been reported. Read More

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Transcriptional landscape of DNA repair genes underpins a pan-cancer prognostic signature associated with cell cycle dysregulation and tumor hypoxia.

DNA Repair (Amst) 2019 06 24;78:142-153. Epub 2019 Apr 24.

Nuffield Department of Medicine, University of Oxford, Old Road Campus, OX3 7FZ, United Kingdom. Electronic address:

Overactive DNA repair contributes to therapeutic resistance in cancer. However, pan-cancer comparative studies investigating the contribution of all DNA repair genes in cancer progression employing an integrated approach have remained limited. We performed a multi-cohort retrospective analysis to determine the prognostic significance of 138 DNA repair genes in 16 cancer types (n = 16,225). Read More

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Is Required for Formation of the Stigma and Style in Rice.

Plant Physiol 2019 06 27;180(2):926-936. Epub 2019 Mar 27.

National Key Laboratory of Crop Genetic Improvement and National Center of Plant Gene Research (Wuhan), Huazhong Agricultural University, Wuhan 430070, China

The stigma is the entry point for sexual reproduction in plants, but the mechanisms underlying stigma development are largely unknown. Here, we disrupted putative auxin biosynthetic and signaling genes to evaluate their roles in rice () development. Disruption of the rice () gene completely eliminated the development of stigmas, and overexpression of led to overproliferation of stigmas, suggesting that is a key determinant for stigma development. Read More

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Derepression of sonic hedgehog signaling upon Gpr161 deletion unravels forebrain and ventricular abnormalities.

Dev Biol 2019 06 23;450(1):47-62. Epub 2019 Mar 23.

Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA. Electronic address:

Inverse gradients of transcriptional repressors antagonize the transcriptional effector response to morphogens. However, the role of such inverse regulation might not manifest solely from lack of repressors. Sonic hedgehog (Shh) patterns the forebrain by being expressed ventrally; however, absence of antagonizing Gli3 repressor paradoxically cause insufficient pathway activation. Read More

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Engineering a conserved RNA regulatory protein repurposes its biological function .

Elife 2019 01 17;8. Epub 2019 Jan 17.

Department of Biological Sciences, University of Texas Dallas, Richardson, United States.

PUF (milio/BF) RNA-binding proteins recognize distinct elements. In , PUF-8 binds to an 8-nt motif and restricts proliferation in the germline. Conversely, FBF-2 recognizes a 9-nt element and promotes mitosis. Read More

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January 2019

A Rice Glutamyl-tRNA Synthetase Modulates Early Anther Cell Division and Patterning.

Plant Physiol 2018 06 2;177(2):728-744. Epub 2018 May 2.

School of Agriculture, Food, and Wine, University of Adelaide, Adelaide, South Australia 5064, Australia

Aminoacyl-tRNA synthetases (aaRSs) have housekeeping roles in protein synthesis, but little is known about how these aaRSs are involved in organ development. Here, we report that a rice () glutamyl-tRNA synthetase (OsERS1) maintains proper somatic cell organization and limits the overproliferation of male germ cells during early anther development. The expression of is specifically detectable in meristematic layer 2-derived cells of the early anther, and anthers exhibit overproliferation and disorganization of layer 2-derived cells, producing fused lobes and extra germ cells in early anthers. Read More

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Graf regulates hematopoiesis through GEEC endocytosis of EGFR.

Development 2017 11 9;144(22):4159-4172. Epub 2017 Oct 9.

Interdisciplinary Graduate Program in Genetic Engineering, Seoul National University, Seoul 08826, Korea

GTPase regulator associated with focal adhesion kinase 1 (GRAF1) is an essential component of the GPI-enriched endocytic compartment (GEEC) endocytosis pathway. Mutations in the human gene are associated with acute myeloid leukemia, but its normal role in myeloid cell development remains unclear. We show that Graf, the ortholog of GRAF1, is expressed and specifically localizes to GEEC endocytic membranes in macrophage-like plasmatocytes. Read More

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November 2017

A Phenotype-Based RNAi Screening for Ras-ERK/MAPK Signaling-Associated Stem Cell Regulators in C. elegans.

Methods Mol Biol 2017 ;1622:207-221

Division of Hematology/Oncology, Department of Medicine, Brody School of Medicine at East Carolina University, Greenville, NC, 27834, USA.

Stem cells have the ability to self-renew and to generate differentiated cell types. A regulatory network that controls this balance is critical for stem cell homeostasis and normal animal development. Particularly, Ras-ERK/MAPK signaling pathway is critical for stem cell self-renewal and differentiation in mammals, including humans. Read More

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prevents class B gene expression and promotes stem cell termination in the fourth whorl of flowers.

Proc Natl Acad Sci U S A 2017 07 20;114(27):7166-7171. Epub 2017 Jun 20.

Department of Biological Sciences, Dartmouth College, Hanover, NH 03755.

The molecular and genetic networks underlying the determination of floral organ identity are well studied, but much less is known about how the flower is partitioned into four developmentally distinct whorls. The gene is required for proper specification of the boundary between stamens in whorl 3 and carpels in whorl 4, as mutants exhibit supernumerary stamens but usually lack carpels. However, it has remained unclear whether extra stamens in mutants originate from an organ identity change in whorl 4 or the overproliferation of whorl 3. Read More

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Dystrophin-glycoprotein complex sequesters Yap to inhibit cardiomyocyte proliferation.

Nature 2017 07 5;547(7662):227-231. Epub 2017 Jun 5.

Cardiomyocyte Renewal Laboratory, Texas Heart Institute, Houston, Texas 77030, USA.

The regenerative capacity of the adult mammalian heart is limited, because of the reduced ability of cardiomyocytes to progress through mitosis. Endogenous cardiomyocytes have regenerative capacity at birth but this capacity is lost postnatally, with subsequent organ growth occurring through cardiomyocyte hypertrophy. The Hippo pathway, a conserved kinase cascade, inhibits cardiomyocyte proliferation in the developing heart to control heart size and prevents regeneration in the adult heart. Read More

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The homolog of Scc4/MAU2 is essential for embryogenesis.

J Cell Sci 2017 03 30;130(6):1051-1063. Epub 2017 Jan 30.

Department of Plant Biology, Uppsala BioCenter, Swedish University of Agricultural Sciences and Linnean Center for Plant Biology, PO Box 7080, Uppsala SE-75007, Sweden

Factors regulating dynamics of chromatin structure have direct impact on expression of genetic information. Cohesin is a multi-subunit protein complex that is crucial for pairing sister chromatids during cell division, DNA repair and regulation of gene transcription and silencing. In non-plant species, cohesin is loaded on chromatin by the Scc2-Scc4 complex (also known as the NIBPL-MAU2 complex). Read More

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Rbf Regulates Drosophila Spermatogenesis via Control of Somatic Stem and Progenitor Cell Fate in the Larval Testis.

Stem Cell Reports 2016 12;7(6):1152-1163

Centre for Stem Cell Systems, Department of Anatomy and Neuroscience, The University of Melbourne, Melbourne, VIC 3010, Australia; Department of Anatomy and Neuroscience, The University of Melbourne, Melbourne, VIC 3010, Australia. Electronic address:

The Drosophila testis has been fundamental to understanding how stem cells interact with their endogenous microenvironment, or niche, to control organ growth in vivo. Here, we report the identification of two independent alleles for the highly conserved tumor suppressor gene, Retinoblastoma-family protein (Rbf), in a screen for testis phenotypes in X chromosome third-instar lethal alleles. Rbf mutant alleles exhibit overproliferation of spermatogonial cells, which is phenocopied by the molecularly characterized Rbf null allele. Read More

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December 2016

Macrophage/monocyte-specific deletion of Ras homolog gene family member A (RhoA) downregulates fractalkine receptor and inhibits chronic rejection of mouse cardiac allografts.

J Heart Lung Transplant 2017 Mar 20;36(3):340-354. Epub 2016 Aug 20.

The Houston Methodist Research Institute, Houston, Texas; Department of Surgery, The Houston Methodist Hospital, Houston, Texas; University of Rennes 1, Faculty of medicine, Rennes, France; The Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston Methodist Hospital, Houston, Texas.

Background: The cellular and molecular mechanisms of chronic rejection of transplanted organs remain obscure; however, macrophages are known to play a critical role in the injury and repair of allografts. Among multiple factors influencing macrophage infiltration to allografts, the fractalkine chemokine (C-X3-C motif) ligand 1(CX3CL1)/chemokine (C-X3-C motif) receptor 1 (CX3CR1) signaling pathway and actin cytoskeleton, which is regulated by a small guanosine-5׳-triphosphatase Ras homolog gene family member A (RhoA), are of the utmost importance. To define the role of macrophage/RhoA pathway involvement in chronic rejection, we generated mice with monocyte/macrophage-specific deletion of RhoA. Read More

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N(6)-Methyladenosine RNA Modification Regulates Shoot Stem Cell Fate in Arabidopsis.

Dev Cell 2016 07 7;38(2):186-200. Epub 2016 Jul 7.

Temasek Life Sciences Laboratory and Department of Biological Sciences, National University of Singapore, 10 Science Drive 4, Singapore 117543, Singapore. Electronic address:

N(6)-Methyladenosine (m(6)A) represents the most prevalent internal modification on mRNA and requires a multicomponent m(6)A methyltransferase complex in mammals. How their plant counterparts determine the global m(6)A modification landscape and its molecular link to plant development remain unknown. Here we show that FKBP12 INTERACTING PROTEIN 37 KD (FIP37) is a core component of the m(6)A methyltransferase complex, which underlies control of shoot stem cell fate in Arabidopsis. Read More

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Regional signals in the planarian body guide stem cell fate in the presence of genomic instability.

Development 2016 05 24;143(10):1697-709. Epub 2016 Mar 24.

Department of Molecular and Cell Biology, School of Natural Sciences, University of California, Merced, CA 95343, USA Quantitative and Systems Biology Graduate Program, University of California, Merced, CA 95343, USA Health Sciences Research Institute, University of California, Merced, CA 95343, USA

Cellular fate decisions are influenced by their topographical location in the adult body. For instance, tissue repair and neoplastic growth are greater in anterior than in posterior regions of adult animals. However, the molecular underpinnings of these regional differences are unknown. Read More

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The Janus soul of centrosomes: a paradoxical role in disease?

Chromosome Res 2016 Jan;24(1):127-44

Institut Curie, PSL Research University, CNRS UMR144, 12 rue Lhomond, 75005, Paris, France.

The centrosome is the main microtubule organizing center of animal cells. It contributes to spindle assembly and orientation during mitosis and to ciliogenesis in interphase. Numerical and structural defects in this organelle are known to be associated with developmental disorders such as dwarfism and microcephaly, but only recently, the molecular mechanisms linking centrosome aberrations to altered physiology are being elucidated. Read More

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January 2016

Fat1 interacts with Fat4 to regulate neural tube closure, neural progenitor proliferation and apical constriction during mouse brain development.

Development 2015 Aug 24;142(16):2781-91. Epub 2015 Jul 24.

Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, M5G 1X5, Canada Department of Molecular Genetics, University of Toronto, Toronto, Ontario, M5S 1A8, Canada

Mammalian brain development requires coordination between neural precursor proliferation, differentiation and cellular organization to create the intricate neuronal networks of the adult brain. Here, we examined the role of the atypical cadherins Fat1 and Fat4 in this process. We show that mutation of Fat1 in mouse embryos causes defects in cranial neural tube closure, accompanied by an increase in the proliferation of cortical precursors and altered apical junctions, with perturbations in apical constriction and actin accumulation. Read More

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Defective Hfp-dependent transcriptional repression of dMYC is fundamental to tissue overgrowth in Drosophila XPB models.

Nat Commun 2015 Jun 15;6:7404. Epub 2015 Jun 15.

Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Melbourne 3010, Australia.

Nucleotide excision DNA repair (NER) pathway mutations cause neurodegenerative and progeroid disorders (xeroderma pigmentosum (XP), Cockayne syndrome (CS) and trichothiodystrophy (TTD)), which are inexplicably associated with (XP) or without (CS/TTD) cancer. Moreover, cancer progression occurs in certain patients, but not others, with similar C-terminal mutations in the XPB helicase subunit of transcription and NER factor TFIIH. Mechanisms driving overproliferation and, therefore, cancer associated with XPB mutations are currently unknown. Read More

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Heixuedian (heix), a potential melanotic tumor suppressor gene, exhibits specific spatial and temporal expression pattern during Drosophila hematopoiesis.

Dev Biol 2015 Feb 18;398(2):218-30. Epub 2014 Dec 18.

Department of Genetics and Developmental Biology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, PR China. Electronic address:

The Drosophila heixuedian (heix) is the ortholog of human UBIAD1 gene (a.k.a TERE1). Read More

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February 2015

Forward genetics identifies Kdf1/1810019J16Rik as an essential regulator of the proliferation-differentiation decision in epidermal progenitor cells.

Dev Biol 2013 Nov 25;383(2):201-13. Epub 2013 Sep 25.

Department of Genetics, Yale University, New Haven, CT 06520, USA.

Cell fate decisions during embryogenesis and adult life govern tissue formation, homeostasis and repair. Two key decisions that must be tightly coordinated are proliferation and differentiation. Overproliferation can lead to hyperplasia or tumor formation while premature differentiation can result in a depletion of proliferating cells and organ failure. Read More

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November 2013

Epigenetic induction of the Ink4a/Arf locus prevents Schwann cell overproliferation during nerve regeneration and after tumorigenic challenge.

Brain 2013 Jul 6;136(Pt 7):2262-78. Epub 2013 Jun 6.

Instituto de Neurociencias de Alicante UMH-CSIC, San Juan de Alicante 03550, Spain.

The number of Schwann cells is fitted to axonal length in peripheral nerves. This relationship is lost when tumorigenic stimuli induce uncontrolled Schwann cell proliferation, generating tumours such us neurofibromas and schwannomas. Schwann cells also re-enter the cell cycle following nerve injury during the process of Wallerian degeneration. Read More

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