Explorer A High-Resolution Anatomical Atlas of the Transcriptome in the Mouse Embryo

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 genomewide 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. 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 PLoS Biology | www.plosbiology. org 1 January 2011 | Volume 9 | Issue 1 | e1000582 * 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