Foxp2 Regulates Anatomical Features That May Be Relevant for Vocal Behaviors and Bipedal Locomotion
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Itcs) in the Mouse Amygdala of Tshz1 Mutants Correlates with Fear, Depression, and Social Interaction Phenotypes
1160 • The Journal of Neuroscience, January 31, 2018 • 38(5):1160–1177 Development/Plasticity/Repair Loss of Intercalated Cells (ITCs) in the Mouse Amygdala of Tshz1 Mutants Correlates with Fear, Depression, and Social Interaction Phenotypes X Jeffrey Kuerbitz,1 Melinda Arnett,5 Sarah Ehrman,1 XMichael T. Williams,3 XCharles V. Vorhees,3 X Simon E. Fisher,6,7 Alistair N. Garratt,8 XLouis J. Muglia,5 Ronald R. Waclaw,1,4 and XKenneth Campbell1,2 Divisions of 1Developmental Biology, 2Neurosurgery, 3Neurology, 4Experimental Hematology and Cancer Biology, 5Center for Prevention of Preterm Birth, Perinatal Institute, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, 6Language and Genetics Department, Max Planck Institute for Psycholinguistics, 6500 AH Nijmegen, The Netherlands, 7Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands, and 8Institute of Cell Biology and Neurobiology, Center for Anatomy, Charite´ University Hospital Berlin, 10117 Berlin, Germany The intercalated cells (ITCs) of the amygdala have been shown to be critical regulatory components of amygdalar circuits, which control appropriate fear responses. Despite this, the molecular processes guiding ITC development remain poorly understood. Here we establish the zinc finger transcription factor Tshz1 as a marker of ITCs during their migration from the dorsal lateral ganglionic eminence through maturity. Using germline and conditional knock-out (cKO) mouse models, we show that Tshz1 is required for the proper migration and differentiation of ITCs. In the absence of Tshz1, migrating ITC precursors fail to settle in their stereotypical locations encapsulating the lateral amygdala and BLA. Furthermore, they display reductions in the ITC marker Foxp2 and ectopic persistence of the dorsal lateral ganglionic eminence marker Sp8. -
Mediator of DNA Damage Checkpoint 1 (MDC1) Is a Novel Estrogen Receptor Co-Regulator in Invasive 6 Lobular Carcinoma of the Breast 7 8 Evelyn K
bioRxiv preprint doi: https://doi.org/10.1101/2020.12.16.423142; this version posted December 16, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. 1 Running Title: MDC1 co-regulates ER in ILC 2 3 Research article 4 5 Mediator of DNA damage checkpoint 1 (MDC1) is a novel estrogen receptor co-regulator in invasive 6 lobular carcinoma of the breast 7 8 Evelyn K. Bordeaux1+, Joseph L. Sottnik1+, Sanjana Mehrotra1, Sarah E. Ferrara2, Andrew E. Goodspeed2,3, James 9 C. Costello2,3, Matthew J. Sikora1 10 11 +EKB and JLS contributed equally to this project. 12 13 Affiliations 14 1Dept. of Pathology, University of Colorado Anschutz Medical Campus 15 2Biostatistics and Bioinformatics Shared Resource, University of Colorado Comprehensive Cancer Center 16 3Dept. of Pharmacology, University of Colorado Anschutz Medical Campus 17 18 Corresponding author 19 Matthew J. Sikora, PhD.; Mail Stop 8104, Research Complex 1 South, Room 5117, 12801 E. 17th Ave.; Aurora, 20 CO 80045. Tel: (303)724-4301; Fax: (303)724-3712; email: [email protected]. Twitter: 21 @mjsikora 22 23 Authors' contributions 24 MJS conceived of the project. MJS, EKB, and JLS designed and performed experiments. JLS developed models 25 for the project. EKB, JLS, SM, and AEG contributed to data analysis and interpretation. SEF, AEG, and JCC 26 developed and performed informatics analyses. MJS wrote the draft manuscript; all authors read and revised the 27 manuscript and have read and approved of this version of the manuscript. -
Open Dogan Phdthesis Final.Pdf
The Pennsylvania State University The Graduate School Eberly College of Science ELUCIDATING BIOLOGICAL FUNCTION OF GENOMIC DNA WITH ROBUST SIGNALS OF BIOCHEMICAL ACTIVITY: INTEGRATIVE GENOME-WIDE STUDIES OF ENHANCERS A Dissertation in Biochemistry, Microbiology and Molecular Biology by Nergiz Dogan © 2014 Nergiz Dogan Submitted in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy August 2014 ii The dissertation of Nergiz Dogan was reviewed and approved* by the following: Ross C. Hardison T. Ming Chu Professor of Biochemistry and Molecular Biology Dissertation Advisor Chair of Committee David S. Gilmour Professor of Molecular and Cell Biology Anton Nekrutenko Professor of Biochemistry and Molecular Biology Robert F. Paulson Professor of Veterinary and Biomedical Sciences Philip Reno Assistant Professor of Antropology Scott B. Selleck Professor and Head of the Department of Biochemistry and Molecular Biology *Signatures are on file in the Graduate School iii ABSTRACT Genome-wide measurements of epigenetic features such as histone modifications, occupancy by transcription factors and coactivators provide the opportunity to understand more globally how genes are regulated. While much effort is being put into integrating the marks from various combinations of features, the contribution of each feature to accuracy of enhancer prediction is not known. We began with predictions of 4,915 candidate erythroid enhancers based on genomic occupancy by TAL1, a key hematopoietic transcription factor that is strongly associated with gene induction in erythroid cells. Seventy of these DNA segments occupied by TAL1 (TAL1 OSs) were tested by transient transfections of cultured hematopoietic cells, and 56% of these were active as enhancers. Sixty-six TAL1 OSs were evaluated in transgenic mouse embryos, and 65% of these were active enhancers in various tissues. -
Prox1regulates the Subtype-Specific Development of Caudal Ganglionic
The Journal of Neuroscience, September 16, 2015 • 35(37):12869–12889 • 12869 Development/Plasticity/Repair Prox1 Regulates the Subtype-Specific Development of Caudal Ganglionic Eminence-Derived GABAergic Cortical Interneurons X Goichi Miyoshi,1 Allison Young,1 Timothy Petros,1 Theofanis Karayannis,1 Melissa McKenzie Chang,1 Alfonso Lavado,2 Tomohiko Iwano,3 Miho Nakajima,4 Hiroki Taniguchi,5 Z. Josh Huang,5 XNathaniel Heintz,4 Guillermo Oliver,2 Fumio Matsuzaki,3 Robert P. Machold,1 and Gord Fishell1 1Department of Neuroscience and Physiology, NYU Neuroscience Institute, Smilow Research Center, New York University School of Medicine, New York, New York 10016, 2Department of Genetics & Tumor Cell Biology, St. Jude Children’s Research Hospital, Memphis, Tennessee 38105, 3Laboratory for Cell Asymmetry, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan, 4Laboratory of Molecular Biology, Howard Hughes Medical Institute, GENSAT Project, The Rockefeller University, New York, New York 10065, and 5Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724 Neurogliaform (RELNϩ) and bipolar (VIPϩ) GABAergic interneurons of the mammalian cerebral cortex provide critical inhibition locally within the superficial layers. While these subtypes are known to originate from the embryonic caudal ganglionic eminence (CGE), the specific genetic programs that direct their positioning, maturation, and integration into the cortical network have not been eluci- dated. Here, we report that in mice expression of the transcription factor Prox1 is selectively maintained in postmitotic CGE-derived cortical interneuron precursors and that loss of Prox1 impairs the integration of these cells into superficial layers. Moreover, Prox1 differentially regulates the postnatal maturation of each specific subtype originating from the CGE (RELN, Calb2/VIP, and VIP). -
And Represses TNF Gene Expression Activating Transcription Factor-2
Histone Deacetylase 3, a Class I Histone Deacetylase, Suppresses MAPK11-Mediated Activating Transcription Factor-2 Activation and Represses TNF Gene Expression This information is current as of September 25, 2021. Ulrich Mahlknecht, Jutta Will, Audrey Varin, Dieter Hoelzer and Georges Herbein J Immunol 2004; 173:3979-3990; ; doi: 10.4049/jimmunol.173.6.3979 http://www.jimmunol.org/content/173/6/3979 Downloaded from References This article cites 45 articles, 31 of which you can access for free at: http://www.jimmunol.org/content/173/6/3979.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 25, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2004 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Histone Deacetylase 3, a Class I Histone Deacetylase, Suppresses MAPK11-Mediated Activating Transcription Factor-2 Activation and Represses TNF Gene Expression1 Ulrich Mahlknecht,2* Jutta Will,* Audrey Varin,† Dieter Hoelzer,* and Georges Herbein2† During inflammatory events, the induction of immediate-early genes, such as TNF-␣, is regulated by signaling cascades including the JAK/STAT, NF-B, and the p38 MAPK pathways, which result in phosphorylation-dependent activation of transcription factors. -
Targeting Endothelial Kruppel-Like Factor 2 (KLF2) in Arteriovenous
Targeting Endothelial Krüppel-like Factor 2 (KLF2) in Arteriovenous Fistula Maturation Failure A dissertation submitted to the Graduate School of the University of Cincinnati in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY (Ph.D.) in the Biomedical Engineering Program Department of Biomedical Engineering College of Engineering and Applied Science 2018 by Keith Louis Saum B.S., Wright State University, 2012 Dissertation Committee: Albert Phillip Owens III, Ph.D. (Committee Chair) Begona Campos-Naciff, Ph.D Christy Holland, Ph.D. Daria Narmoneva, Ph.D. Prabir Roy-Chaudhury, M.D., Ph.D Charuhas Thakar, M.D. Abstract The arteriovenous fistula (AVF) is the preferred form of vascular access for hemodialysis. However, 25-60% of AVFs fail to mature to a state suitable for clinical use, resulting in significant morbidity, mortality, and cost for end-stage renal disease (ESRD) patients. AVF maturation failure is recognized to result from changes in local hemodynamics following fistula creation which lead to venous stenosis and thrombosis. In particular, abnormal wall shear stress (WSS) is thought to be a key stimulus which alters endothelial function and promotes AVF failure. In recent years, the transcription factor Krüppel-like factor-2 (KLF2) has emerged as a key regulator of endothelial function, and reduced KLF2 expression has been shown to correlate with disturbed WSS and AVF failure. Given KLF2’s importance in regulating endothelial function, the objective of this dissertation was to investigate how KLF2 expression is regulated by the hemodynamic and uremic stimuli within AVFs and determine if loss of endothelial KLF2 is responsible for impaired endothelial function. -
An Unbiased Reconstruction of the T Helper Cell Type 2 Differentiation Network
bioRxiv preprint doi: https://doi.org/10.1101/196022; this version posted October 4, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. An unbiased reconstruction of the T helper cell type 2 differentiation network 1,3 1 1 1 1 Authors: Johan Henriksson , Xi Chen , Tomás Gomes , Kerstin Meyer , Ricardo Miragaia , 4 1 4 1 1,2,* Ubaid Ullah , Jhuma Pramanik , Riita Lahesmaa , Kosuke Yusa , Sarah A Teichmann Affiliations: 1 Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, United Kingdom 2 EMBL-European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, United Kingdom 3 Karolinska Institutet, Department. of Biosciences and Nutrition, Hälsovägen 7, Novum, SE-141 83, Huddinge, Sweden 4 Turku Centre for Biotechnology, Tykistokatu 6 FI-20520, Turku, Finland *To whom correspondence should be addressed: [email protected] Tomas: [email protected] Ricardo: [email protected] Ubaid Ullah: [email protected] Jhuma: [email protected] -
Global Mef2 Target Gene Analysis in Skeletal and Cardiac Muscle
GLOBAL MEF2 TARGET GENE ANALYSIS IN SKELETAL AND CARDIAC MUSCLE STEPHANIE ELIZABETH WALES A DISSERTATION SUBMITTED TO THE FACULTY OF GRADUATE STUDIES IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY GRADUATE PROGRAM IN BIOLOGY YORK UNIVERSITY TORONTO, ONTARIO FEBRUARY 2016 © Stephanie Wales 2016 ABSTRACT A loss of muscle mass or function occurs in many genetic and acquired pathologies such as heart disease, sarcopenia and cachexia which are predominantly found among the rapidly increasing elderly population. Developing effective treatments relies on understanding the genetic networks that control these disease pathways. Transcription factors occupy an essential position as regulators of gene expression. Myocyte enhancer factor 2 (MEF2) is an important transcription factor in striated muscle development in the embryo, skeletal muscle maintenance in the adult and cardiomyocyte survival and hypertrophy in the progression to heart failure. We sought to identify common MEF2 target genes in these two types of striated muscles using chromatin immunoprecipitation and next generation sequencing (ChIP-seq) and transcriptome profiling (RNA-seq). Using a cell culture model of skeletal muscle (C2C12) and primary cardiomyocytes we found 294 common MEF2A binding sites within both cell types. Individually MEF2A was recruited to approximately 2700 and 1600 DNA sequences in skeletal and cardiac muscle, respectively. Two genes were chosen for further study: DUSP6 and Hspb7. DUSP6, an ERK1/2 specific phosphatase, was negatively regulated by MEF2 in a p38MAPK dependent manner in striated muscle. Furthermore siRNA mediated gene silencing showed that MEF2D in particular was responsible for repressing DUSP6 during C2C12 myoblast differentiation. Using a p38 pharmacological inhibitor (SB 203580) we observed that MEF2D must be phosphorylated by p38 to repress DUSP6. -
Cortical Foxp2 Supports Behavioral Flexibility and Developmental Dopamine D1 Receptor Expression
bioRxiv preprint doi: https://doi.org/10.1101/624973; this version posted May 2, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Cortical Foxp2 supports behavioral flexibility and developmental dopamine D1 receptor expression Marissa Co, Stephanie L. Hickey, Ashwinikumar Kulkarni, Matthew Harper, Genevieve Konopka* Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA *Correspondence: [email protected] Contact information Genevieve Konopka, Ph.D. Department of Neuroscience, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., ND4.300, Dallas, TX 75390-9111 TEL: 214-648-5135, FAX: 214-648-1801, Email: [email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/624973; this version posted May 2, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Abstract FoxP2 encodes a forkhead box transcription factor required for the development of neural circuits underlying language, vocalization, and motor-skill learning. Human genetic studies have associated FOXP2 variation with neurodevelopmental disorders (NDDs), and within the cortex, it is coexpressed and interacts with other NDD-associated transcription factors. Cortical Foxp2 is required in mice for proper social interactions, but its role in other NDD-relevant behaviors and molecular pathways is unknown. -
The MER41 Family of Hervs Is Uniquely Involved in the Immune-Mediated Regulation of Cognition/Behavior-Related Genes
bioRxiv preprint doi: https://doi.org/10.1101/434209; this version posted October 3, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. The MER41 family of HERVs is uniquely involved in the immune-mediated regulation of cognition/behavior-related genes: pathophysiological implications for autism spectrum disorders Serge Nataf*1, 2, 3, Juan Uriagereka4 and Antonio Benitez-Burraco 5 1CarMeN Laboratory, INSERM U1060, INRA U1397, INSA de Lyon, Lyon-Sud Faculty of Medicine, University of Lyon, Pierre-Bénite, France. 2 University of Lyon 1, Lyon, France. 3Banque de Tissus et de Cellules des Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France. 4Department of Linguistics and School of Languages, Literatures & Cultures, University of Maryland, College Park, USA. 5Department of Spanish, Linguistics, and Theory of Literature (Linguistics). Faculty of Philology. University of Seville, Seville, Spain * Corresponding author: [email protected] bioRxiv preprint doi: https://doi.org/10.1101/434209; this version posted October 3, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. ABSTRACT Interferon-gamma (IFNa prototypical T lymphocyte-derived pro-inflammatory cytokine, was recently shown to shape social behavior and neuronal connectivity in rodents. STAT1 (Signal Transducer And Activator Of Transcription 1) is a transcription factor (TF) crucially involved in the IFN pathway. -
The Untold Stories of the Speech Gene, the FOXP2 Cancer Gene
www.Genes&Cancer.com Genes & Cancer, Vol. 9 (1-2), January 2018 The untold stories of the speech gene, the FOXP2 cancer gene Maria Jesus Herrero1,* and Yorick Gitton2,* 1 Center for Neuroscience Research, Children’s National Medical Center, NW, Washington, DC, USA 2 Sorbonne University, INSERM, CNRS, Vision Institute Research Center, Paris, France * Both authors contributed equally to this work Correspondence to: Yorick Gitton, email: [email protected] Keywords: FOXP2 factor, oncogene, cancer, prognosis, language Received: March 01, 2018 Accepted: April 02, 2018 Published: April 18, 2018 Copyright: Herrero and Gitton et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT FOXP2 encodes a transcription factor involved in speech and language acquisition. Growing evidence now suggests that dysregulated FOXP2 activity may also be instrumental in human oncogenesis, along the lines of other cardinal developmental transcription factors such as DLX5 and DLX6 [1–4]. Several FOXP family members are directly involved during cancer initiation, maintenance and progression in the adult [5–8]. This may comprise either a pro- oncogenic activity or a deficient tumor-suppressor role, depending upon cell types and associated signaling pathways. While FOXP2 is expressed in numerous cell types, its expression has been found to be down-regulated in breast cancer [9], hepatocellular carcinoma [8] and gastric cancer biopsies [10]. Conversely, overexpressed FOXP2 has been reported in multiple myelomas, MGUS (Monoclonal Gammopathy of Undetermined Significance), several subtypes of lymphomas [5,11], as well as in neuroblastomas [12] and ERG fusion-negative prostate cancers [13]. -
Foxp2 Loss of Function Increases Striatal Direct Pathway Inhibition Via Increased GABA Release
Brain Structure and Function https://doi.org/10.1007/s00429-018-1746-6 ORIGINAL ARTICLE Foxp2 loss of function increases striatal direct pathway inhibition via increased GABA release Jon‑Ruben van Rhijn1,2,3 · Simon E. Fisher3,4 · Sonja C. Vernes2,4 · Nael Nadif Kasri1,5 Received: 8 March 2018 / Accepted: 31 August 2018 © The Author(s) 2018 Abstract Heterozygous mutations of the Forkhead-box protein 2 (FOXP2) gene in humans cause childhood apraxia of speech. Loss of Foxp2 in mice is known to affect striatal development and impair motor skills. However, it is unknown if striatal excitatory/ inhibitory balance is affected during development and if the imbalance persists into adulthood. We investigated the effect of reduced Foxp2 expression, via a loss-of-function mutation, on striatal medium spiny neurons (MSNs). Our data show that heterozygous loss of Foxp2 decreases excitatory (AMPA receptor-mediated) and increases inhibitory (GABA receptor-medi- ated) currents in D1 dopamine receptor positive MSNs of juvenile and adult mice. Furthermore, reduced Foxp2 expression increases GAD67 expression, leading to both increased presynaptic content and release of GABA. Finally, pharmacological blockade of inhibitory activity in vivo partially rescues motor skill learning deficits in heterozygous Foxp2 mice. Our results suggest a novel role for Foxp2 in the regulation of striatal direct pathway activity through managing inhibitory drive. Keywords Foxp2 · Excitatory-inhibitory balance · Neurodevelopment · D1R-MSN · Striatum Introduction Balanced neuronal activity between cortex, striatum and Sonja C. Vernes and Nael Nadif Kasri contributed equally to this thalamus is essential for the generation of voluntary move- work. ments (Shepherd 2013). Imbalanced activity within the stria- tum is known to disrupt complex motor behaviors, such as Electronic supplementary material The online version of this the production of spoken language (Peach 2004; Square- article (https ://doi.org/10.1007/s0042 9-018-1746-6) contains supplementary material, which is available to authorized users.