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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

Expression patterns of modules associated with ages and regions. Line plot for four modules related to region (A) and four related to age (B). The left plots show the developmental profiles of each module, plotted separately for each brain region (using different colors). X-axes show the developmental stages, while y-axes show the value of eigengene (PC1) for each module. Adjacent plots show the top 5 GO pathways associated with each module, with some redundant categories filtered. Bars show the significance of each category. Vertical red lines indicate nominal P = 0.05.
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DDV166F4: Expression patterns of modules associated with ages and regions. Line plot for four modules related to region (A) and four related to age (B). The left plots show the developmental profiles of each module, plotted separately for each brain region (using different colors). X-axes show the developmental stages, while y-axes show the value of eigengene (PC1) for each module. Adjacent plots show the top 5 GO pathways associated with each module, with some redundant categories filtered. Bars show the significance of each category. Vertical red lines indicate nominal P = 0.05.

Mentions: We identified individual modules that showed strong associations with age and brain region, and were associated with specific developmental processes or cellular functions (Fig. 4). In many cases, the regional patterning was already established at birth and persisted through development. For example, module M21 was highly expressed in neocortical regions, and showed a slight increase in expression with time (Fig. 4A). The dense neuronal make-up of the cortex was reflected in GO enrichment of genes in this module including synapse, neuron projection and other neuron-associated GO categories. Genes associated with M21 were significantly enriched for transcription factors (17 genes, P = 0.008). ‘Hub’ genes of a module are often highly biologically relevant, either by playing a functional role (39,40) or by marking a cell type or cellular process with high specificity (41). Hub genes for this module included CUX2 and SATB2, two key transcription factors for the proper specification of upper cortical layer neurons (42).Figure 4.


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)

Expression patterns of modules associated with ages and regions. Line plot for four modules related to region (A) and four related to age (B). The left plots show the developmental profiles of each module, plotted separately for each brain region (using different colors). X-axes show the developmental stages, while y-axes show the value of eigengene (PC1) for each module. Adjacent plots show the top 5 GO pathways associated with each module, with some redundant categories filtered. Bars show the significance of each category. Vertical red lines indicate nominal P = 0.05.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492396&req=5

DDV166F4: Expression patterns of modules associated with ages and regions. Line plot for four modules related to region (A) and four related to age (B). The left plots show the developmental profiles of each module, plotted separately for each brain region (using different colors). X-axes show the developmental stages, while y-axes show the value of eigengene (PC1) for each module. Adjacent plots show the top 5 GO pathways associated with each module, with some redundant categories filtered. Bars show the significance of each category. Vertical red lines indicate nominal P = 0.05.
Mentions: We identified individual modules that showed strong associations with age and brain region, and were associated with specific developmental processes or cellular functions (Fig. 4). In many cases, the regional patterning was already established at birth and persisted through development. For example, module M21 was highly expressed in neocortical regions, and showed a slight increase in expression with time (Fig. 4A). The dense neuronal make-up of the cortex was reflected in GO enrichment of genes in this module including synapse, neuron projection and other neuron-associated GO categories. Genes associated with M21 were significantly enriched for transcription factors (17 genes, P = 0.008). ‘Hub’ genes of a module are often highly biologically relevant, either by playing a functional role (39,40) or by marking a cell type or cellular process with high specificity (41). Hub genes for this module included CUX2 and SATB2, two key transcription factors for the proper specification of upper cortical layer neurons (42).Figure 4.

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