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A Transcriptomic Atlas of Mouse Neocortical Layers

ABSTRACT: In the mammalian cortex, neurons and glia form a patterned structure across six layers whose complex cytoarchitectonic arrangement likely contributes greatly to cognitive abilities. We sequenced transcriptomes from layers 1-6b of the adult (P56) mouse primary somatosensory cortex, along with dorsal cortex and lateral cortex, to understand the transcriptional levels and functional repertoires of coding and noncoding loci for cells that constitute these layers. 5,835 protein-coding genes and 66 noncoding RNA loci are differentially expressed (patterned) across the layers, based on a machine-learning model (naive Bayes) approach. Layers 2-6b are each associated with specific functional and disease annotations that provide insights into their biological roles. This new resource greatly extends currently available resources, such as the Allen Mouse Brain Atlas and microarray data sets, by providing quantitative expression levels, by being genome-wide, by including novel loci, and by identifying alternatively spliced transcripts that are differentially expressed across layers.

ORGANISM(S): Mus musculus

PROVIDER: GSE27243 | GEO | 2011/08/24

SECONDARY ACCESSION(S): PRJNA137171

REPOSITORIES: GEO

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Project description:Genome-wide transcriptional profiling allows characterization of the molecular underpinnings of neocortical organization, including cortical areal specialization, laminar cell type diversity and functional anatomy. Microarray analysis of individual cortical layers across sensorimotor and association cortices in rhesus macaque demonstrated robust and specific laminar and areal molecular signatures driven by differential expression of genes associated with specialized neuronal function. Gene expression corresponding with laminar architecture was generally similar across cortical areas, although genes with robust areal patterning were often highly laminar as well, and these patterns were more highly conserved between macaque and human as compared to mouse. Layer 4 of primate primary visual cortex displayed a distinct molecular signature compared to other cortical regions, a specialization not observed in mouse. Overall, transcriptome-based relationships were strongest between proximal layers in a cortical area, and between neighboring areas along the rostrocaudal axis, reflecting in vivo cortical spatial topography and therefore a developmental imprint. Tissue from male and female monkeys (n = 2-3 animals/gender) was collected from anterior cingulate gyrus (ACG), layers 2, 3, 5, 6; orbitofrontal cortex (OFC), layers 2, 3, 5, 6; dorsolateral prefrontal cortex (DLPFC), layers 2-6; primary motor cortex (M1), layers 2, 3, 5, 6; primary somatosensory cortex (S1), layers 2-6; primary auditory cortex (A1), layers 2-6; primary visual cortex (V1), layers 2-6 including 4A, 4B, 4Calpha (4Ca), 4Cbeta (4Cb); secondary visual cortex (V2), layers 2-6; middle temporal area (MT), layers 2-6; temporal area (TE), layers 2-6; hippocampus, CA1, CA2, CA3, dentate gyrus (DG); and dorsal lateral geniculate nucleus (LGN), magnocellular, parvocellular and koniocellular divisions. Due to the limited number of samples that could be amplified concurrently, amplifications were performed in 3 batches (batches A-C, containing 102, 119 and 10 experimental samples, respectively). To control for batch effects, common RNA pool control samples were amplified and hybridized in each batch. These included LCM extracted hippocampus CA3 samples from the current study and a whole rhesus brain RNA pool (Biochain). These control samples were hybridized in 6 replicates in batch A and B and in 3 replicates in batch C (3 replicates per 96 well plate).

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A Transcriptomic Atlas of Mouse Neocortical Layers

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