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Spatiotemporal dynamics of the postnatal developing primate brain transcriptome.

Bakken TE, Miller JA, Luo R, Bernard A, Bennett JL, Lee CK, Bertagnolli D, Parikshak NN, Smith KA, Sunkin SM, Amaral DG, Geschwind DH, Lein ES - Hum. Mol. Genet. (2015)

Bottom Line: Neocortex showed significantly greater differential expression over time than subcortical structures, and this trend likely reflects the protracted postnatal development of the cortex.In particular, one module with high expression in neonatal cortex and striatum that decreases during infancy and juvenile development was significantly enriched for autism spectrum disorder (ASD)-related genes.This network was enriched for genes associated with axon guidance and interneuron differentiation, consistent with a disruption in the formation of functional cortical circuitry in ASD.

View Article: PubMed Central - PubMed

Affiliation: Allen Institute for Brain Science, Seattle, WA, USA.

No MeSH data available.


Related in: MedlinePlus

Developmental transcriptional profiles common to and unique between brain regions. (A) Venn-diagram shows the overlap of age-associated genes identified in neocortex and the three non-neocortical areas. (B) Overlap between genes DE in visual cortex and medial prefrontal cortex. (C) Heatmaps show age-associated genes unique to each brain region. Samples are in columns and ordered by age. Genes are presented on the rows, sorted such that genes decreasing with age are on top and genes increasing with age are at the bottom. Gene symbols for selected transcription factors are displayed in the right margins. Red indicates high expression and green indicates low expression.
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DDV166F2: Developmental transcriptional profiles common to and unique between brain regions. (A) Venn-diagram shows the overlap of age-associated genes identified in neocortex and the three non-neocortical areas. (B) Overlap between genes DE in visual cortex and medial prefrontal cortex. (C) Heatmaps show age-associated genes unique to each brain region. Samples are in columns and ordered by age. Genes are presented on the rows, sorted such that genes decreasing with age are on top and genes increasing with age are at the bottom. Gene symbols for selected transcription factors are displayed in the right margins. Red indicates high expression and green indicates low expression.

Mentions: We next sought to understand how gene expression dynamics vary between different brain regions. We conducted five one-way ANOVAs—one for each region—to identify genes DE with age (FDR < 0.05, fold-change >2 in any pair of four ages; see Materials and Methods and Supplemental Material, Table S3). The largest number of DE probes was found in neocortex (2983 probes combining visual and medial prefrontal areas) and hippocampus (745). In contrast, 500 probes were DE in amygdala and only 101 probes in ventral striatum, perhaps reflecting relatively earlier prenatal genesis of these regions. Surprisingly, ∼80% of DE probes were specific to a region, while only 20% were shared between any pair of regions (Fig. 2A). For example, 2342 probes were changing with age selectively in neocortex and GO enrichment analysis suggested significant involvement of cell adhesion (P = 1.8 × 10−11) and calcium ion binding (P = 5.5 × 10−9) (see Supplementary Material, Table S3 for a full list of GO enrichment terms).Figure 2.


Spatiotemporal dynamics of the postnatal developing primate brain transcriptome.

Bakken TE, Miller JA, Luo R, Bernard A, Bennett JL, Lee CK, Bertagnolli D, Parikshak NN, Smith KA, Sunkin SM, Amaral DG, Geschwind DH, Lein ES - Hum. Mol. Genet. (2015)

Developmental transcriptional profiles common to and unique between brain regions. (A) Venn-diagram shows the overlap of age-associated genes identified in neocortex and the three non-neocortical areas. (B) Overlap between genes DE in visual cortex and medial prefrontal cortex. (C) Heatmaps show age-associated genes unique to each brain region. Samples are in columns and ordered by age. Genes are presented on the rows, sorted such that genes decreasing with age are on top and genes increasing with age are at the bottom. Gene symbols for selected transcription factors are displayed in the right margins. Red indicates high expression and green indicates low expression.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
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getmorefigures.php?uid=PMC4492396&req=5

DDV166F2: Developmental transcriptional profiles common to and unique between brain regions. (A) Venn-diagram shows the overlap of age-associated genes identified in neocortex and the three non-neocortical areas. (B) Overlap between genes DE in visual cortex and medial prefrontal cortex. (C) Heatmaps show age-associated genes unique to each brain region. Samples are in columns and ordered by age. Genes are presented on the rows, sorted such that genes decreasing with age are on top and genes increasing with age are at the bottom. Gene symbols for selected transcription factors are displayed in the right margins. Red indicates high expression and green indicates low expression.
Mentions: We next sought to understand how gene expression dynamics vary between different brain regions. We conducted five one-way ANOVAs—one for each region—to identify genes DE with age (FDR < 0.05, fold-change >2 in any pair of four ages; see Materials and Methods and Supplemental Material, Table S3). The largest number of DE probes was found in neocortex (2983 probes combining visual and medial prefrontal areas) and hippocampus (745). In contrast, 500 probes were DE in amygdala and only 101 probes in ventral striatum, perhaps reflecting relatively earlier prenatal genesis of these regions. Surprisingly, ∼80% of DE probes were specific to a region, while only 20% were shared between any pair of regions (Fig. 2A). For example, 2342 probes were changing with age selectively in neocortex and GO enrichment analysis suggested significant involvement of cell adhesion (P = 1.8 × 10−11) and calcium ion binding (P = 5.5 × 10−9) (see Supplementary Material, Table S3 for a full list of GO enrichment terms).Figure 2.

Bottom Line: Neocortex showed significantly greater differential expression over time than subcortical structures, and this trend likely reflects the protracted postnatal development of the cortex.In particular, one module with high expression in neonatal cortex and striatum that decreases during infancy and juvenile development was significantly enriched for autism spectrum disorder (ASD)-related genes.This network was enriched for genes associated with axon guidance and interneuron differentiation, consistent with a disruption in the formation of functional cortical circuitry in ASD.

View Article: PubMed Central - PubMed

Affiliation: Allen Institute for Brain Science, Seattle, WA, USA.

No MeSH data available.


Related in: MedlinePlus