Atlas of an Organism: Gene Expression in Developing Mouse Embryo
ScienceDaily (Jan. 18, 2011) — While every cell of an organism contains the same genes only a proportion are expressed in any tissue at a given stage in development. Knowing the extent of gene transcription is valuable and a team of European researchers has generated an atlas of gene expression for the developing mouse embryo. This will be a powerful resource to determine co-expression of genes and to identify functional associations between genes relevant to development and disease.
The findings are published in the online, open access journal PLoS Biology.
The comprehensive, interactive and freely accessible digital gene expression atlas (www.eurexpress.org) includes expression data for over 15,000 genes in hundreds of anatomical structures and led to the identification of tissue-specific and tissue-overlapping gene networks. For instance the data revealed new information for several developing structures, such as the telencephalon, a novel organization for the hypothalamus and insight on the signaling pathways involved in renal epithelial differentiation during kidney development.
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A High-Resolution Anatomical Atlas of the Transcriptome in the Mouse Embryo
Graciana Diez-Roux1, Sandro Banfi1, Marc Sultan2, Lars Geffers3, Santosh Anand1, David Rozado2, Alon Magen2,Elena Canidio4, Massimiliano Pagani4¤a, Ivana Peluso1,Nathalie Lin-Marq5, Muriel Koch6, Marchesa Bilio1,Immacolata Cantiello1, Roberta Verde1, Cristian De Masi1,Salvatore A. Bianchi1, Juliette Cicchini5, Elodie Perroud5,Shprese Mehmeti5, Emilie Dagand2, Sabine Schrinner2, Asja Nürnberger2, Katja Schmidt2, Katja Metz2, Christina Zwingmann2, Norbert Brieske2, Cindy Springer2, Ana Martinez Hernandez3, Sarah Herzog3, Frauke Grabbe3,Cornelia Sieverding3, Barbara Fischer3, Kathrin Schrader3,Maren Brockmeyer3, Sarah Dettmer3, Christin Helbig3,Violaine Alunni6, Marie-Annick Battaini6, Carole Mura6, Charlotte N. Henrichsen7, Raquel Garcia-Lopez8, Diego Echevarria8, Eduardo Puelles8, Elena Garcia-Calero8, Stefan Kruse9, Markus Uhr3, Christine Kauck3, Guangjie Feng10, Nestor Milyaev10, Chuang Kee Ong10, Lalit Kumar10, MeiSze Lam10, Colin A. Semple10, Attila Gyenesei10¤b, Stefan Mundlos2, Uwe Radelof11¤c, Hans Lehrach2, Paolo Sarmientos4, Alexandre Reymond7,Duncan R. Davidson10*, Pascal Dollé12*, Stylianos E. Antonarakis5,13*, Marie-Laure Yaspo2*, Salvador Martinez8*, Richard A. Baldock10*, Gregor Eichele3*, Andrea Ballabio1,14,15,16*
1 Telethon Institute of Genetics and Medicine, Naples, Italy, 2 Max Planck Institute for Molecular Genetics, Berlin, Germany, 3 Genes and Behavior Department, Max Planck Institute of Biophysical Chemistry, Goettingen, Germany,4 Primm, Milan, Italy, 5 Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland, 6 Institut Clinique de la Souris, Illkirch, France, 7 Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland, 8 Experimental Embryology Lab, Instituto de Neurociencias, Universidad Miguel Hernandez, San Juan de Alicante, Spain, 9 ORGARAT, Essen, Germany, 10 Medical Research Council Human Genetics Unit, Western General Hospital, Edinburgh, United Kingdom, 11 RZPD—Deutsches Ressourcenzentrum für Genomforschung, Berlin, Germany, 12 Institut de Génétique et de Biologie Moléculaire et Cellulaire, Inserm U 964, CNRS UMR 7104, Faculté de Médecine, Université de Strasbourg; Illkirch, France, 13 University Hospitals of Geneva, Geneva, Switzerland, 14 Medical Genetics, Department of Pediatrics, Federico II University, Naples, Italy, 15Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America, 16 Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, Texas, United States of America
Abstract
Ascertaining when and where genes are expressed is of crucial importance to understanding or predicting the physiological role of genes and proteins and how they interact to form the complex networks that underlie organ development and function. It is, therefore, crucial to determine on a genome-wide level, the spatio-temporal gene expression profiles at cellular resolution. This information is provided by colorimetric RNA in situ hybridization that can elucidate expression of genes in their native context and does so at cellular resolution. We generated what is to our knowledge the first genome-wide transcriptome atlas by RNA in situ hybridization of an entire mammalian organism, the developing mouse at embryonic day 14.5. This digital transcriptome atlas, the Eurexpress atlas (http://www.eurexpress.org), consists of a searchable database of annotated images that can be interactively viewed. We generated anatomy-based expression profiles for over 18,000 coding genes and over 400 microRNAs. We identified 1,002 tissue-specific genes that are a source of novel tissue-specific markers for 37 different anatomical structures. The quality and the resolution of the data revealed novel molecular domains for several developing structures, such as the telencephalon, a novel organization for the hypothalamus, and insight on the Wnt network involved in renal epithelial differentiation during kidney development. The digital transcriptome atlas is a powerful resource to determine co-expression of genes, to identify cell populations and lineages, and to identify functional associations between genes relevant to development and disease.
Author Summary
In situ hybridization (ISH) can be used to visualize gene expression in cells and tissues in their native context. High-throughput ISH using nonradioactive RNA probes allowed the Eurexpress consortium to generate a comprehensive, interactive, and freely accessible digital gene expression atlas, the Eurexpress transcriptome atlas (http://www.eurexpress.org), of the E14.5 mouse embryo. Expression data for over 15,000 genes were annotated for hundreds of anatomical structures, thus allowing us to systematically identify tissue-specific and tissue-overlapping gene networks. We illustrate the value of the Eurexpress atlas by finding novel regional subdivisions in the developing brain. We also use the transcriptome atlas to allocate specific components of the complex Wnt signaling pathway to kidney development, and we identify regionally expressed genes in liver that may be markers of hematopoietic stem cell differentiation.
Citation: Diez-Roux G, Banfi S, Sultan M, Geffers L, Anand S, et al. (2011) A High-Resolution Anatomical Atlas of the Transcriptome in the Mouse Embryo. PLoS Biol 9(1): e1000582. doi:10.1371/journal.pbio.1000582
Academic Editor: Gregory S. Barsh, Stanford University, United States of America
Received: August 4, 2010; Accepted: December 6, 2010; Published: January 18, 2011
Copyright: © 2010 Diez-Roux et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported by the EC VI Framework Programme contract number LSHG-CT-2004-512003. The authors also acknowledge the support of: the Italian Telethon Foundation (AB, SB, and GD-R); the Swiss National Science Foundation (AR and SEA); the Max Planck Society (GE, M-LY, HL); MRC (RB, DD); Association pour la Recherche sur le Cancer (PD); and Ingenio 2010 MEC-CONSOLIDER CSD2007-00023, DIGESIC-MEC BFU2008-00588, CIBERSAM/ISCIII (SM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Abbreviations: ABA, Allen Brain Atlas; AH, anterior hypothalamic; CNS, central nervous system; E[number], embryonic day [number]; EMAGE, Edinburgh Mouse Atlas of Gene Expression; EMAP, Edinburgh Mouse Atlas Project; FIATAS, Fast Image Annotation Software; GO, Gene Ontology; HSC, hematopoietic stem cell; ISH, in situ hybridization; MGI, Mouse Genome Informatics; TM, tuberomammillar
* E-mail: Duncan.Davidson@hgu.mrc.ac.uk (DRD); dolle@igbmc.fr (PD); stylianos.antonarakis@unige.ch(SEA); Yaspo@molgen.mpg.de (M-LY); smartinez@umh.es (SM); Richard.Baldock@hgu.mrc.ac.uk (RAB);Gregor.Eichele@mpibpc.mpg.de (GE); ballabio@tigem.it (AB)
¤a Current address: Istituto Nazionale di Genetica Molecolare, Milan, Italy
¤b Current address: Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland
¤c Current address: Scienion, Berlin, Germany
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