A Transcriptomic Atlas of Mouse Neocortical Layers

T Grant Belgard,Ana C Marques,Peter L Oliver,Hatice Ozel Abaan,Tamara M Sirey,Anna Hoerder-Suabedissen,Fernando García-Moreno,Zoltán Molnár,Elliott H Margulies,Chris P Ponting

doi:10.1016/j.neuron.2011.06.039

T Grant Belgard, Ana C Marques + Show 8 more

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SummaryIn the mammalian cortex, neurons and glia form a patterned structure across six layers whose complex cytoarchitectonic arrangement is likely to contribute to cognition. We sequenced transcriptomes from layers 1-6b of different areas (primary and secondary) of the adult (postnatal day 56) mouse somatosensory cortex to understand the transcriptional levels and functional repertoires of coding and noncoding loci for cells constituting these layers. A total of 5,835 protein-coding genes and 66 noncoding RNA loci are differentially expressed (“patterned”) across the layers, on the basis of 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 (http://genserv.anat.ox.ac.uk/layers) 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 candidate alternatively spliced transcripts that are differentially expressed across layers.

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Comparative and pathological studies suggest the mammalian cerebral cortex to be the anatomical substrate of higher cognitive functions including language, episodic memory, and voluntary movement (Jones and Rakic, 2010; Kaas, 2008; Rakic, 2009)
RNA samples A-F were derived from six adjacent laminar segments of mouse primary somatosensory cortex (S1) from two sets of four littermates dissected under a binocular microscope with a microsurgical scalpel (Figure 1A)
Half of all transcripts derived from just 2% of expressed genes and the most highly expressed genes were generally of mitochondrial origin. 10% of mouse genome sequence located outside of known protein-coding, pseudogene, tRNA, rRNA, and short RNA gene loci, was expressed in at least one sample, including 1,055 long intergenic noncoding loci (Table S1; Belgard et al, 2011) (Ponting et al, 2009)

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Comparative and pathological studies suggest the mammalian cerebral cortex to be the anatomical substrate of higher cognitive functions including language, episodic memory, and voluntary movement (Jones and Rakic, 2010; Kaas, 2008; Rakic, 2009). The cerebral cortex has a uniform laminar structure that historically has been divided into six layers (Brodmann, 1909). The upper layers (1 to 4) form localized intracortical connections (Gilbert and Wiesel, 1979; Toyama et al, 1974) and are thought to process information locally. The deep layers of the cortex, 5 and 6, form longer-distance projections to subcortical targets (including the thalamus, striatum, basal pons, tectum, and spinal cord) and to the opposite hemisphere. Some layer 5 neurons are among the largest cells of the brain and exhibit the longest connections. Layer 6b in mouse neocortex is a distinct sublamina with characteristic connections, gene expression patterns, and physiological properties (Hoerder-Suabedissen et al, 2009; Kanold and Luhmann, 2010)

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