An anatomic gene expression atlas of the adult mouse brain

Ng, Lydia; Bernard, Amy; C, Lau; Overly, Caroline C.; Dong, Hong‐Wei; Kuan, Chihchau; Pathak, Dev S.; Sunkin, Susan M.; Dang, Chinh; Bohland, Jason W.; Bokil, Hemant; Mitra, Partha P.; Puelles, Luis; Hohmann, John G.; Anderson, David J.; Lein, Ed; Jones, Allan R.; Hawrylycz, Michael

doi:10.1038/nn.2281

Cited by 277 publications

(292 citation statements)

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“…Although Meis3 seems to have a more restricted expression pattern than the other two Meis genes in mouse, Xenopus, and zebrafish (Waskiewicz et al, 2001;Ng et al, 2009), it has been implicated in several developmental processes in these species (Dibner et al, 2001(Dibner et al, , 2004Aamar and Frank, 2004;diIorio et al, 2007;Manfroid et al, 2007;Elkouby et al, 2010;Gutkovich et al, 2010). However, these roles could represent evolutionary novelties or cooptions in these lineages or, alternatively, could have been taken over by the other Meis genes in birds.…”

Section: Discussionmentioning

confidence: 99%

Distinct and redundant expression and transcriptional diversity of MEIS gene paralogs during chicken development

Sánchez-Guardado

Irimia

Sánchez-Arrones

et al. 2011

Developmental Dynamics

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Members of the Meis family of TALE homeobox transcription factors are involved in many processes of vertebrate development and morphogenesis, showing extremely complex transcriptional and spatiotemporal expression patterns. In this work, we performed a comprehensive study of chicken Meis genes using multiple approaches. First, we assessed whether the chicken genome contains a Meis3 ortholog or harbors only two Meis genes; we gathered several lines of evidence pointing to a specific loss of the Meis3 ortholog in an early ancestor of birds. Next, we studied the transcriptional diversity generated from chicken Meis genes through alternative splicing during development. Finally, we performed a detailed analysis of chick Meis1/ 2 expression patterns during early embryogenesis and organogenesis. We show that the expression of both Meis genes begins at the gastrulation stage in the three embryonic layers, presenting highly dynamic patterns with overlapping as well as distinct expression domains throughout development. Developmental Dynamics 240:1475-1492, 2011. V C 2011 Wiley-Liss, Inc.Key words: TALE family; alternative splicing; ectoderm; mesoderm; endoderm; central nervous system; sensory organs; visceral development; gut Accepted 17 January 2011 Developmental DynamicsABBREVIATIONS A atrium aip anterior intestinal portal as alternative splicing av allantoic vesicle ba branchial arches bd bile duct C conotruncus cl cloaca cnp caudal neural plate co coelom cp cardiac primordium D diencephalon da dorsal aorta dh dorsal horn dm dermomyotome dp dorsal pancreas du duodenum ect ectoderm ep ephiphysis end endoderm Eo-PmC extraocular pre-muscle cluster FB forebrain fg foregut fp floor plate Hn Hensen node HB hindbrain Hyp hypothalamus inf infundibulum isth isthmus l lens ltl larynx-trachea-lug bud lpm lateral plate mesoderm lp lens placode lv liver lb lung bud MB midbrain Mes mesencephalon mes mesoderm mg mid-gut mn mesonephric system mp mandibular process MRB mesencephalic-rhombencephalic boundary nep nephrotome nf neural fold np neural plate nr neural retina nt notochord oc otic cup oe oesophagus of optic furrow omv omphalomensenteric vena os optic stalk ot otocyst ov optic vesicle p prosomere p1 prosomere 1 p2 prosomere 2 p3 prosomere 3 pc pericardial cavity pe pigmented epithelium pf primitive fold pg primitive groove ph pharynx pm precardiac mesoderm POA preoptic area pp prechordal plate ps primitive streak psm primitive streak mesoderm PT pretectum Rh rhombencephalon rh rhombomere RhA1 rhombomere A1 rnp rostral neural plate Rp Rathke's pouch rp roof plate SC spinal cord scl sclerotome sm somatic mesoderm smp somatopleure som somite SP secondary prosencephalon sp segmental plate spm splanchnic mesoderm spp splanchnopleure st stomach sub.p subcephalic pocket sv sinus venosus tb tail bud td thyro-glossal duct Tel telencephalon TH thalamus Tv telencephalic vesicle V.n trigeminal ganglion V ventricle WGS whole genome shotgun zli zona limitans intrathalamica

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Section: Discussionmentioning

confidence: 99%

Distinct and redundant expression and transcriptional diversity of MEIS gene paralogs during chicken development

Sánchez-Guardado

Irimia

Sánchez-Arrones

et al. 2011

Developmental Dynamics

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“…The Anatomic Gene Expression Atlas (AGEA) in principle enables users to view a comprehensive list of genes expressed in any given three-dimensional voxel of the mouse brain atlas by using the Gene Finder application. 15) Expression levels in different brain regions were downloaded as xml files and processed with Microsoft Excel 2007. Sagittal planes of the spinal cord were taken at the cervical spinal level (C1) for further analysis of Dnpep, Resp18, and Ptprn expression data.…”

Section: Methodsmentioning

confidence: 99%

Aspartyl Aminopeptidase, Encoded by an Evolutionarily Conserved Syntenic Gene, Is Colocalized with Its Cluster in Secretory Granules of Pancreatic Islet Cells

Cai

Wang

Chen

2010

Bioscience, Biotechnology, and Biochemistry

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“…This has enabled analysis of the spatial correlation structure of gene expression (7)(8)(9)(10)(11)(12). In the Allen Brain Atlas (ABA) of the adult mouse, the brain is divided up into cubic voxels of size 200 μm.…”

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confidence: 99%

“…[24][25][26]. The entry Eðv; gÞ is the expression energy of the gene labeled g in the voxel labeled v [a measure representing the level of mRNA in situ hybridization (1,10)]. We combine the ABA with cell-type-specific transcriptome profiles, to gain biological understanding of the coexpression patterns of the genes.…”

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confidence: 99%

Cell-type–based model explaining coexpression patterns of genes in the brain

Grange

Bohland

Okaty

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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125

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Spatial patterns of gene expression in the vertebrate brain are not independent, as pairs of genes can exhibit complex patterns of coexpression. Two genes may be similarly expressed in one region, but differentially expressed in other regions. These correlations have been studied quantitatively, particularly for the Allen Atlas of the adult mouse brain, but their biological meaning remains obscure. We propose a simple model of the coexpression patterns in terms of spatial distributions of underlying cell types and establish its plausibility using independently measured cell-typespecific transcriptomes. The model allows us to predict the spatial distribution of cell types in the mouse brain.neuroscience | bioinformatics | neuroanatomy B rain-wide and genome-wide maps of gene expression are now available (1, 2), due to the development of high-throughput neuroanatomical methods (3-6). This has enabled analysis of the spatial correlation structure of gene expression (7-12). In the Allen Brain Atlas (ABA) of the adult mouse, the brain is divided up into cubic voxels of size 200 μm. The expression energies of up to 20,000 genes in the adult C57BL/6J mouse are given by automatic processing of in situ hybridized (ISH) brain sections, coregistered to the Allen Reference Atlas (ARA) (13). Coexpression of two genes in a voxel may arise from two sources: ðiÞ both genes are expressed within the same cell type or ðiiÞ the two genes are expressed in two different cell types, both present in the voxel. These two possibilities cannot be disentangled solely on the basis of the ABA. Ideally, gene expression profiles should be experimentally obtained for each cell type in the brain, and indeed such transcriptome profiles are now available (14-21). This cell-based approach to the study of gene expression is complementary to the gene-based approach of the ABA. In ref. 22, the data of ref. 19 were used to extract neuron-specific genes, astrocyte-specific genes, and oligodendrocyte-specific genes, which resulted in three combinations of brain-wide maps from the ABA, whose clustering showed anatomical signatures of major brain subdivisions (see also ref. 23 for estimates of neuron-specific and oligodendrocyte-specific expression patterns, both in the mouse and in the human brain). The present paper goes beyond the broad classification of cell types into three classes and attempts to estimate density profiles of every cell type known by its transcriptome profile. To study the genes collectively we use a voxel-by-gene data matrix E, corresponding to V = 49;742 cubic voxels, and 3,041 genes, as in refs. 24-26. The entry Eðv; gÞ is the expression energy of the gene labeled g in the voxel labeled v [a measure representing the level of mRNA in situ hybridization (1, 10)]. We combine the ABA with cell-type-specific transcriptome profiles, to gain biological understanding of the coexpression patterns of the genes. Our model is based on G = 2;131 genes found in all these datasets and in the coronal ABA. The model proposed to estimate the brain-w...

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An anatomic gene expression atlas of the adult mouse brain

Cited by 277 publications

References 28 publications

Distinct and redundant expression and transcriptional diversity of MEIS gene paralogs during chicken development

Distinct and redundant expression and transcriptional diversity of MEIS gene paralogs during chicken development

Aspartyl Aminopeptidase, Encoded by an Evolutionarily Conserved Syntenic Gene, Is Colocalized with Its Cluster in Secretory Granules of Pancreatic Islet Cells

Cell-type–based model explaining coexpression patterns of genes in the brain

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