A Prominent Couple
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
The Function of the Zinc Finger Transcription Factor Insm1 in Neuronal Progenitors Madeleine Julie Larrosa
The function of the zinc finger transcription factor Insm1 in neuronal progenitors Inaugural-Dissertation To obtain the academic degree Doctor rerum naturalium (Dr. rer. nat.) Submitted to the Department of Biology, Chemistry and Pharmacy of Freie Universität Berlin By Madeleine Julie Larrosa From Paris 2019 This work was carried out at the Max Delbrück Centrum for Molecular Medicine in Berlin from November 2015 to October 2019 under the supervision of Prof. Dr. Carmen Birchmeier and Prof. Dr. Holger Gerhardt. 1st Reviewer: Prof. Dr. Holger Gerhardt 2nd Reviewer: Prof. Dr. Stephan Sigrist Date of PhD Defense: This doctoral thesis is dedicated to my mother Juliette Ban, who offered unconditional love and endless devotion, and taught me to work hard for the things I aspire to achieve. I also dedicate this work to Mohammed Marine, who has been a constant source of support and encouragement, and without whom I would not have completed this doctoral thesis. In loving memory of my friend Lorelei Arbeille, who taught me to never give up through her incredible strength and perseverance. Statement of contribution I confirm that the work presented in this doctoral thesis is my own and that all information derived from other sources is indicated. Madlen Sohn, technician in the group of Prof. Dr. Wei Chen at the MDC, performed the sequencing of the immunoprecipitated chromatin and the transcriptome for the ChIP-seq and RNA-seq experiments, respectively. Dr. Mahmoud Ibrahim and Dr. Scott Lacadie, bioinformaticians in the group of Prof. Dr. Uwe Ohler at the MDC, analyzed the ChIP-seq data and Dr. -
Functional Analysis of the Homeobox Gene Tur-2 During Mouse Embryogenesis
Functional Analysis of The Homeobox Gene Tur-2 During Mouse Embryogenesis Shao Jun Tang A thesis submitted in conformity with the requirements for the Degree of Doctor of Philosophy Graduate Department of Molecular and Medical Genetics University of Toronto March, 1998 Copyright by Shao Jun Tang (1998) National Library Bibriothèque nationale du Canada Acquisitions and Acquisitions et Bibiiographic Services seMces bibliographiques 395 Wellington Street 395, rue Weifington OtbawaON K1AW OttawaON KYAON4 Canada Canada The author has granted a non- L'auteur a accordé une licence non exclusive licence alIowing the exclusive permettant à la National Library of Canada to Bibliothèque nationale du Canada de reproduce, loan, distri%uteor sell reproduire, prêter' distribuer ou copies of this thesis in microform, vendre des copies de cette thèse sous paper or electronic formats. la forme de microfiche/nlm, de reproduction sur papier ou sur format électronique. The author retains ownership of the L'auteur conserve la propriété du copyright in this thesis. Neither the droit d'auteur qui protège cette thèse. thesis nor substantial extracts fkom it Ni la thèse ni des extraits substantiels may be printed or otherwise de celle-ci ne doivent être imprimés reproduced without the author's ou autrement reproduits sans son permission. autorisation. Functional Analysis of The Homeobox Gene TLr-2 During Mouse Embryogenesis Doctor of Philosophy (1998) Shao Jun Tang Graduate Department of Moiecular and Medicd Genetics University of Toronto Abstract This thesis describes the clonhg of the TLx-2 homeobox gene, the determination of its developmental expression, the characterization of its fiuiction in mouse mesodem and penpheral nervous system (PNS) developrnent, the regulation of nx-2 expression in the early mouse embryo by BMP signalling, and the modulation of the function of nX-2 protein by the 14-3-3 signalling protein during neural development. -
Ptf1a/Rbpj Complex Inhibits Ganglion Cell Fate and Drives the Specification of All Horizontal Cell Subtypes in the Chick Retina
Ptf1a/Rbpj complex inhibits ganglion cell fate and drives the specification of all horizontal cell subtypes in the chick retina. Elise Lelièvre, Monkol Lek, Henrik Boije, L. Houille-Vernes, Valérie Brajeul, A. Slembrouck, Jérôme Roger, José-Alain Sahel, Jean-Marc Matter, Florian Sennlaub, et al. To cite this version: Elise Lelièvre, Monkol Lek, Henrik Boije, L. Houille-Vernes, Valérie Brajeul, et al.. Ptf1a/Rbpj complex inhibits ganglion cell fate and drives the specification of all horizontal cell subtypes in the chick retina.: Ptf1a in chick retinal development. Developmental Biology, Elsevier, 2011, 358 (2), pp.296-308. 10.1016/j.ydbio.2011.07.033. inserm-00614775 HAL Id: inserm-00614775 https://www.hal.inserm.fr/inserm-00614775 Submitted on 16 Aug 2011 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Ptf1a/Rbpj complex inhibits ganglion cell fate and drives the specification of all horizontal cell subtypes in the chick retina. 1,2,3,4,5 6 6 2,4,5 2,4,5 E.C. Lelièvre , M. Lek , H. Boije , L. Houille-Verne s , V. Brajeul , A. Slembrouck2,4,5, J.E. Roger4, J. Sahel2,4,5, J.M. -
Integrating Single-Step GWAS and Bipartite Networks Reconstruction Provides Novel Insights Into Yearling Weight and Carcass Traits in Hanwoo Beef Cattle
animals Article Integrating Single-Step GWAS and Bipartite Networks Reconstruction Provides Novel Insights into Yearling Weight and Carcass Traits in Hanwoo Beef Cattle Masoumeh Naserkheil 1 , Abolfazl Bahrami 1 , Deukhwan Lee 2,* and Hossein Mehrban 3 1 Department of Animal Science, University College of Agriculture and Natural Resources, University of Tehran, Karaj 77871-31587, Iran; [email protected] (M.N.); [email protected] (A.B.) 2 Department of Animal Life and Environment Sciences, Hankyong National University, Jungang-ro 327, Anseong-si, Gyeonggi-do 17579, Korea 3 Department of Animal Science, Shahrekord University, Shahrekord 88186-34141, Iran; [email protected] * Correspondence: [email protected]; Tel.: +82-31-670-5091 Received: 25 August 2020; Accepted: 6 October 2020; Published: 9 October 2020 Simple Summary: Hanwoo is an indigenous cattle breed in Korea and popular for meat production owing to its rapid growth and high-quality meat. Its yearling weight and carcass traits (backfat thickness, carcass weight, eye muscle area, and marbling score) are economically important for the selection of young and proven bulls. In recent decades, the advent of high throughput genotyping technologies has made it possible to perform genome-wide association studies (GWAS) for the detection of genomic regions associated with traits of economic interest in different species. In this study, we conducted a weighted single-step genome-wide association study which combines all genotypes, phenotypes and pedigree data in one step (ssGBLUP). It allows for the use of all SNPs simultaneously along with all phenotypes from genotyped and ungenotyped animals. Our results revealed 33 relevant genomic regions related to the traits of interest. -
Modulation of the Activity of a Key Metabolic Regulator Small Heterodimer Partner by Post-Translational Modifications
MODULATION OF THE ACTIVITY OF A KEY METABOLIC REGULATOR SMALL HETERODIMER PARTNER BY POST-TRANSLATIONAL MODIFICATIONS BY DEEPTHI KANAMALURU DISSERTATION Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biochemistry in the Graduate College of the University of Illinois at Urbana-Champaign, 2011 Urbana, Illinois Doctoral Committee: Associate Professor Jongsook Kim Kemper, Chair Professor David J. Shapiro Professor Milan K. Bagchi Assistant Professor Lin-Feng Chen Abstract Small Heterodimer Partner (SHP, NR0B2), a member of the nuclear receptor superfamily, is an orphan receptor that lacks a DNA binding domain but contains a putative ligand binding domain. SHP forms non-functional heterodimers with DNA binding transcriptional factors and, thereby, functions as a transcriptional corepressor in diverse biological processes, including cellular metabolism, cell proliferation, apoptosis, and sexual maturation. Of these reported functions of SHP, maintaining cholesterol and bile acid levels by negative feedback regulation of hepatic conversion of cholesterol to bile acids is well established. Cholesterol is essential in many biological activities in mammalian cells. Conversion of hepatic cholesterol into bile acids is a major pathway to eliminate cholesterol from the body. However, excess amounts of cholesterol and bile acids are pathogenic. Therefore, the levels of cholesterol and bile acids need to be tightly regulated. Cholesterol 7α-hydroxylase (CYP7A1), a liver specific P450 enzyme, is the first and rate-limiting enzyme in this process. Increased levels of bile acids repress transcription of CYP7A1 in a feedback manner. In response to elevated bile acid levels, the nuclear bile acid receptor Farnesoid X Receptor (FXR) increases the transcription of SHP. -
Dynamic Transcriptomic Profiles of Zebrafish Gills in Response to Zinc
Zheng et al. BMC Genomics 2010, 11:548 http://www.biomedcentral.com/1471-2164/11/548 RESEARCH ARTICLE Open Access Dynamic transcriptomic profiles of zebrafish gills in response to zinc depletion Dongling Zheng1,4, Peter Kille2, Graham P Feeney2, Phil Cunningham1, Richard D Handy3, Christer Hogstrand1* Abstract Background: Zinc deficiency is detrimental to organisms, highlighting its role as an essential micronutrient contributing to numerous biological processes. To investigate the underlying molecular events invoked by zinc depletion we performed a temporal analysis of transcriptome changes observed within the zebrafish gill. This tissue represents a model system for studying ion absorption across polarised epithelial cells as it provides a major pathway for fish to acquire zinc directly from water whilst sharing a conserved zinc transporting system with mammals. Results: Zebrafish were treated with either zinc-depleted (water = 2.61 μgL-1; diet = 26 mg kg-1) or zinc-adequate (water = 16.3 μgL-1; diet = 233 mg kg-1) conditions for two weeks. Gill samples were collected at five time points and transcriptome changes analysed in quintuplicate using a 16K oligonucleotide array. Of the genes represented the expression of a total of 333 transcripts showed differential regulation by zinc depletion (having a fold-change greater than 1.8 and an adjusted P-value less than 0.1, controlling for a 10% False Discovery Rate). Down-regulation was dominant at most time points and distinct sets of genes were regulated at different stages. Annotation enrichment analysis revealed that ‘Developmental Process’ was the most significantly overrepresented Biological Process GO term (P = 0.0006), involving 26% of all regulated genes. -
Discovering Mechanisms That Regulate Beta-Cell Neogenesis
DISCOVERING MECHANISMS THAT REGULATE BETA-CELL NEOGENESIS AND PROLIFERATION by Hannah Elizabeth Edelman A dissertation submitted to Johns Hopkins University in conformity with the requirements for the degree of Doctor of Philosophy Baltimore, Maryland November 2018 ABSTRACT In both Type I and Type II diabetes, a loss of functioning beta cells results in an inability to produce insulin effectively to regulate blood glucose. Current treatments have a variety of problems including insulin-dependence, donor scarcity, comorbidities, and cost. We are interested in inducing the body to produce its own beta cells endogenously by either neogenesis from progenitors or proliferation of existing beta cells. From previous work, we know that the transcription factor Sox9b plays an important role in the identity of endocrine progenitor cells in the zebrafish pancreas, known as centroacinar cells (CACs), that contribute to regeneration of beta cells. Since humans also have CACs but do not regenerate efficiently, we wanted to understand the downstream targets of Sox9b/SOX9 and their role in the biology of CACs. Using RNA-seq and ChIP-seq in PANC-1 cells we were able to find direct targets of SOX9, including the interesting candidate EPCAM, to follow up on. For assessing beta-cell proliferation, we knew from a previous screen that selective serotonin reuptake inhibitors (SSRIs) can induce beta-cell proliferation in the larval zebrafish. We hypothesized that innervation of the principal islet was responsible for this serotonergic signaling to the pancreas. Using imaging of a variety of transgenic lines, we established that innervation of the islet occurs by 4 days post fertilization and that the sox10 mutant zebrafish has a reduced amount of this innervation. -
Forkhead Transcription Factors and Ageing
Oncogene (2008) 27, 2351–2363 & 2008 Nature Publishing Group All rights reserved 0950-9232/08 $30.00 www.nature.com/onc REVIEW Forkhead transcription factors and ageing L Partridge1 and JC Bru¨ ning2 1Institute of Healthy Ageing, GEE, London, UK; 2Department of Mouse Genetics and Metabolism, Institute for Genetics University of Cologne, Cologne, Germany Mutations in single genes and environmental interventions Forkhead transcription factors are turning out to play can extend healthy lifespan in laboratory model organi- a key role in invertebrate models ofextension ofhealthy sms. Some of the mechanisms involved show evolutionary lifespan by single-gene mutations, and evidence is conservation, opening the way to using simpler inverte- mounting for their importance in mammals. Forkheads brates to understand human ageing. Forkhead transcrip- can also play a role in extension oflifespanby dietary tion factors have been found to play a key role in lifespan restriction, an environmental intervention that also extension by alterations in the insulin/IGF pathway and extends lifespan in diverse organisms (Kennedy et al., by dietary restriction. Interventions that extend lifespan 2007). Here, we discuss these findings and their have also been found to delay or ameliorate the impact of implications. The forkhead family of transcription ageing-related pathology and disease, including cancer. factors is characterized by a type of DNA-binding Understanding the mode of action of forkheads in this domain known as the forkhead box (FOX) (Weigel and context will illuminate the mechanisms by which ageing Jackle, 1990). They are also called winged helix acts as a risk factor for ageing-related disease, and could transcription factors because of the crystal structure lead to the development of a broad-spectrum, preventative ofthe FOX, ofwhich the forkheadscontain a medicine for the diseases of ageing. -
Mouse Insm1 Conditional Knockout Project (CRISPR/Cas9)
http://www.alphaknockout.com/ Mouse Insm1 Conditional Knockout Project (CRISPR/Cas9) Objective: To create a Insm1 conditional knockout mouse model (C57BL/6J) by CRISPR/Cas-mediated genome engineering. Strategy summary: The Insm1 gene ( NCBI Reference Sequence: NM_016889 ; Ensembl: ENSMUSG00000068154 ) is located on mouse chromosome 2. 1 exon is identified , with the ATG start codon in exon 1 and the TAG stop codon in exon 1 (Transcript: ENSMUST00000089257). Exon 1 will be selected as conditional knockout region (cKO region). Deletion of this region should result in the loss of function of the mouse Insm1 gene. To engineer the targeting vector, homologous arms and cKO region will be generated by PCR using BAC clone RP23-114P5 as template. Cas9, gRNA and targeting vector will be co-injected into fertilized eggs for cKO mouse production. The pups will be genotyped by PCR followed by sequencing analysis. Note: Mice homozygous for a null allele display perinatal and neonatal lethality, respiratory failure, and impaired pancreatic and intestinal endocrine cell development. Exon 1 starts from the start codon. The knockout of Exon 1 cover 100% of the coding region. The size of effective cKO region: ~3232 bp. This strategy is designed based on genetic information in existing databases. Due to the complexity of biological processes, all risk of loxP insertion on gene transcription, RNA splicing and protein translation cannot be predicted at existing technological level. Page 1 of 7 http://www.alphaknockout.com/ Overview of the Targeting Strategy gRNA region Wildtype allele A T 5' G gRNA region 3' 1 Targeting vector A T G Targeted allele A T G Constitutive KO allele (After Cre recombination) Legends Homology arm Exon of mouse Insm1 cKO region loxP site Page 2 of 7 http://www.alphaknockout.com/ Overview of the Dot Plot Window size: 10 bp Forward Reverse Complement Sequence 12 Note: The sequence of homologous arms and cKO region is aligned with itself to determine if there are tandem repeats. -
Generation of Retinal Neurons: Focus on the Proliferation And
"They misunderestimated me" George W Bush (2000) List of Papers This thesis is based on the following papers, which are referred to in the text by their Roman numerals. I Edqvist, P.H.D., Lek, M., Boije, H., Lindbäck, S.M., Hallböök, F. (2008) Axon-bearing and axon-less horizontal cell subtypes are generated consecutively during chick retinal development from progenitors that are sensitive to follistatin. BMC Developmental Biology, 8:46-67 II Boije, H., Edqvist, P.H.D., Hallböök, F. (2009) Horizontal cell progenitors arrest in G2-phase and undergo terminal mitosis on the vitreal side of the chick retina. Developmental Biology, 330: 105-113 III Fard, S.S., Boije, H., Hallböök, F. (2011) The terminal mitosis of chicken retinal horizontal cells is preceded by a G2-phase arrest that relies on the cyclin B1-Cdk1 complex but is independent of DNA damage. (Submitted to The Journal of Neuroscience) IV Boije, H., Edqvist, P.H., Hallböök, F. (2008) Temporal and spatial expression of transcription factors FoxN4, Ptf1a, Prox1, Isl1 and Lim1 mRNA in the developing chick retina. Gene Expression Patterns, 8:117-123 V Lelièvre, E., Lek, M., Boije, H., Houille, L., Brajeul, V., Slembrouck, A., Sahel, J., Matter, J.M., Sennlaub, F., Hallböök, F., Goureau, O., Guillonneau, X. (2011) Ptf1a/Rbpj complex inhibits ganglion cell fate by downregulating Atoh7 and drives the specification of all horizontal cell subtypes in the chick retina. (Submitted to Developmental Biology) VI Boije, H., Fard, S.S., Ring, H., Hallböök, F. (2011) FoxN4 is sufficient for commitment to the retinal horizontal cell fate and is able to instigate differentiation programs in neural progenitors. -
Integrative Epigenomic and Genomic Analysis of Malignant Pheochromocytoma
EXPERIMENTAL and MOLECULAR MEDICINE, Vol. 42, No. 7, 484-502, July 2010 Integrative epigenomic and genomic analysis of malignant pheochromocytoma Johanna Sandgren1,2* Robin Andersson3*, pression examination in a malignant pheochromocy- Alvaro Rada-Iglesias3, Stefan Enroth3, toma sample. The integrated analysis of the tumor ex- Goran̈ Akerstro̊ m̈ 1, Jan P. Dumanski2, pression levels, in relation to normal adrenal medulla, Jan Komorowski3,4, Gunnar Westin1 and indicated that either histone modifications or chromo- somal alterations, or both, have great impact on the ex- Claes Wadelius2,5 pression of a substantial fraction of the genes in the in- vestigated sample. Candidate tumor suppressor 1Department of Surgical Sciences genes identified with decreased expression, a Uppsala University, Uppsala University Hospital H3K27me3 mark and/or in regions of deletion were for SE-75185 Uppsala, Sweden 2 instance TGIF1, DSC3, TNFRSF10B, RASSF2, HOXA9, Department of Genetics and Pathology Rudbeck Laboratory, Uppsala University PTPRE and CDH11. More genes were found with in- SE-75185 Uppsala, Sweden creased expression, a H3K4me3 mark, and/or in re- 3The Linnaeus Centre for Bioinformatics gions of gain. Potential oncogenes detected among Uppsala University those were GNAS, INSM1, DOK5, ETV1, RET, NTRK1, SE-751 24 Uppsala, Sweden IGF2, and the H3K27 trimethylase gene EZH2. Our ap- 4Interdisciplinary Centre for Mathematical and proach to associate histone methylations and DNA Computational Modelling copy number changes to gene expression revealed ap- Warsaw University parent impact on global gene transcription, and en- PL-02-106 Warszawa, Poland abled the identification of candidate tumor genes for 5Corresponding author: Tel, 46-18-471-40-76; further exploration. -
Comparative Transcriptomics Reveals Similarities and Differences
Seifert et al. BMC Cancer (2015) 15:952 DOI 10.1186/s12885-015-1939-9 RESEARCH ARTICLE Open Access Comparative transcriptomics reveals similarities and differences between astrocytoma grades Michael Seifert1,2,5*, Martin Garbe1, Betty Friedrich1,3, Michel Mittelbronn4 and Barbara Klink5,6,7 Abstract Background: Astrocytomas are the most common primary brain tumors distinguished into four histological grades. Molecular analyses of individual astrocytoma grades have revealed detailed insights into genetic, transcriptomic and epigenetic alterations. This provides an excellent basis to identify similarities and differences between astrocytoma grades. Methods: We utilized public omics data of all four astrocytoma grades focusing on pilocytic astrocytomas (PA I), diffuse astrocytomas (AS II), anaplastic astrocytomas (AS III) and glioblastomas (GBM IV) to identify similarities and differences using well-established bioinformatics and systems biology approaches. We further validated the expression and localization of Ang2 involved in angiogenesis using immunohistochemistry. Results: Our analyses show similarities and differences between astrocytoma grades at the level of individual genes, signaling pathways and regulatory networks. We identified many differentially expressed genes that were either exclusively observed in a specific astrocytoma grade or commonly affected in specific subsets of astrocytoma grades in comparison to normal brain. Further, the number of differentially expressed genes generally increased with the astrocytoma grade with one major exception. The cytokine receptor pathway showed nearly the same number of differentially expressed genes in PA I and GBM IV and was further characterized by a significant overlap of commonly altered genes and an exclusive enrichment of overexpressed cancer genes in GBM IV. Additional analyses revealed a strong exclusive overexpression of CX3CL1 (fractalkine) and its receptor CX3CR1 in PA I possibly contributing to the absence of invasive growth.