Limits...
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

Module M12 is associated with ASD candidate genes. (A) VisANT plot showing the top 200 connections in M12. The hub genes, which have more connections, are displayed in the inner circle. Purple nodes indicate genes identified as ASD candidate genes from SFARI Base, with the remaining nodes shown in green. (B) Heatmap of the expression patterns for two hub genes in module M12. Cell colors show the average expression of samples from the specified age (y-axis) and region (x-axis).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

DDV166F5: Module M12 is associated with ASD candidate genes. (A) VisANT plot showing the top 200 connections in M12. The hub genes, which have more connections, are displayed in the inner circle. Purple nodes indicate genes identified as ASD candidate genes from SFARI Base, with the remaining nodes shown in green. (B) Heatmap of the expression patterns for two hub genes in module M12. Cell colors show the average expression of samples from the specified age (y-axis) and region (x-axis).

Mentions: Intriguingly, module M12 did not show even nominally significant overlap with ASD modules from Parikshak et al., suggesting a novel role for striatum in the neuropathology of ASD. To understand the co-expression relationships of the genes within M12, we created a network diagram based on the top 200 connections (based on co-expression) between pairs of genes (Fig. 5A). This network included six genes from SFARI (PTCHD1, FOXP1, NRXN3, LAMB1, PCDH10 and GALNT13), two of which are hub genes. Figure 5B shows decreasing expression with age in neocortex and striatum for the hub genes PTCHD1, a receptor for sonic hedgehog, and FOXP1, a forkhead box transcription factor (Fig. 5B). Rare mutations in FOXP1 have been linked to ASD and other disorders associated with ID and mental retardation (54). Together this demonstrates that a number of genes associated with ASD are coordinately expressed across postnatal development, both in the neocortex and the striatum.Figure 5.


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)

Module M12 is associated with ASD candidate genes. (A) VisANT plot showing the top 200 connections in M12. The hub genes, which have more connections, are displayed in the inner circle. Purple nodes indicate genes identified as ASD candidate genes from SFARI Base, with the remaining nodes shown in green. (B) Heatmap of the expression patterns for two hub genes in module M12. Cell colors show the average expression of samples from the specified age (y-axis) and region (x-axis).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

DDV166F5: Module M12 is associated with ASD candidate genes. (A) VisANT plot showing the top 200 connections in M12. The hub genes, which have more connections, are displayed in the inner circle. Purple nodes indicate genes identified as ASD candidate genes from SFARI Base, with the remaining nodes shown in green. (B) Heatmap of the expression patterns for two hub genes in module M12. Cell colors show the average expression of samples from the specified age (y-axis) and region (x-axis).
Mentions: Intriguingly, module M12 did not show even nominally significant overlap with ASD modules from Parikshak et al., suggesting a novel role for striatum in the neuropathology of ASD. To understand the co-expression relationships of the genes within M12, we created a network diagram based on the top 200 connections (based on co-expression) between pairs of genes (Fig. 5A). This network included six genes from SFARI (PTCHD1, FOXP1, NRXN3, LAMB1, PCDH10 and GALNT13), two of which are hub genes. Figure 5B shows decreasing expression with age in neocortex and striatum for the hub genes PTCHD1, a receptor for sonic hedgehog, and FOXP1, a forkhead box transcription factor (Fig. 5B). Rare mutations in FOXP1 have been linked to ASD and other disorders associated with ID and mental retardation (54). Together this demonstrates that a number of genes associated with ASD are coordinately expressed across postnatal development, both in the neocortex and the striatum.Figure 5.

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