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Gene expression in the rat brain: high similarity but unique differences between frontomedial-, temporal- and occipital cortex.

Stansberg C, Ersland KM, van der Valk P, Steen VM - BMC Neurosci (2011)

Bottom Line: A large proportion of these 65 genes appear to be involved in signal transduction, including the ion channel Fxyd6, the neuropeptide Grp and the nuclear receptor Rorb.We also find that the majority of these genes display increased expression levels around birth and show distinct preferences for certain cortical layers and cell types in rodents.Since specific patterns of expression often are linked to equally specialised biological functions, we propose that these cortex sub-region enriched genes are important for proper functioning of the cortical regions in question.

View Article: PubMed Central - HTML - PubMed

Affiliation: Dr E. Martens Research Group for Biological Psychiatry, Department of Clinical Medicine, University of Bergen, Norway. Christine.Stansberg@uib.no

ABSTRACT

Background: The six-layered neocortex of the mammalian brain may appear largely homologous, but is in reality a modular structure of anatomically and functionally distinct areas. However, global gene expression seems to be almost identical across the cerebral cortex and only a few genes have so far been reported to show regional enrichment in specific cortical areas.

Results: In the present study on adult rat brain, we have corroborated the strikingly similar gene expression among cortical areas. However, differential expression analysis has allowed for the identification of 30, 24 and 11 genes enriched in frontomedial -, temporal- or occipital cortex, respectively. A large proportion of these 65 genes appear to be involved in signal transduction, including the ion channel Fxyd6, the neuropeptide Grp and the nuclear receptor Rorb. We also find that the majority of these genes display increased expression levels around birth and show distinct preferences for certain cortical layers and cell types in rodents.

Conclusions: Since specific patterns of expression often are linked to equally specialised biological functions, we propose that these cortex sub-region enriched genes are important for proper functioning of the cortical regions in question.

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Spatial and time-dependent expression patterns of genes enriched in OCx. Expression profiles for 4 selected genes in rat brain regions, across different stages of the developing cortex, in astrocytes, oligodendrocytes and neurons and in different neuronal subtypes, as well as laminar expression patterns of the regional genes in their corresponding cortical regions. Profiles (a-d) were generated based on microarray data obtained from [20] (a), [10] (b), [28] (c) and [30] (d). Individual samples, including replicates, are placed along the x-axis. The y-axis indicates normalised signal intensities for each gene in each individual sample. Simple profiles are presented for illustration purposes; full profiles with detailed expression levels and sample information are available as additional material. In situ hybridisation images (e) were downloaded from the Allen Mouse Brain Atlas. FMCx, fronto-medial cortex; TCx, temporal cortex; OCx, occipital cortex.; HiF, Hippocampus; Str, Striatum; Cb, cerebellum; Oligo, oligodendrocytes; Astro, astrocytes; Glu, Glutamatergic neurons; GABA, GABAergic neurons; CgCx, cingulated cortex; SSCx, somatosensory cortex; n.a., not available; * arrows indicate increasingly mature cells
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Figure 4: Spatial and time-dependent expression patterns of genes enriched in OCx. Expression profiles for 4 selected genes in rat brain regions, across different stages of the developing cortex, in astrocytes, oligodendrocytes and neurons and in different neuronal subtypes, as well as laminar expression patterns of the regional genes in their corresponding cortical regions. Profiles (a-d) were generated based on microarray data obtained from [20] (a), [10] (b), [28] (c) and [30] (d). Individual samples, including replicates, are placed along the x-axis. The y-axis indicates normalised signal intensities for each gene in each individual sample. Simple profiles are presented for illustration purposes; full profiles with detailed expression levels and sample information are available as additional material. In situ hybridisation images (e) were downloaded from the Allen Mouse Brain Atlas. FMCx, fronto-medial cortex; TCx, temporal cortex; OCx, occipital cortex.; HiF, Hippocampus; Str, Striatum; Cb, cerebellum; Oligo, oligodendrocytes; Astro, astrocytes; Glu, Glutamatergic neurons; GABA, GABAergic neurons; CgCx, cingulated cortex; SSCx, somatosensory cortex; n.a., not available; * arrows indicate increasingly mature cells

Mentions: After strict manual inspection of all FDR = 0 selected expression profiles, a total of 65 genes were ultimately determined as being markedly enriched in either FMCx, TCx or OCx, of which 54 were supported in both data sets. Nine of the AB1700-generated genes could not be confirmed in the Illumina data, either due to non-representation on the Illumina RatRef-12 array (Aldh3b2, C1ql3, rCG46329, rCG41008, RGD1306921 and Mab21/l) or lack of significant enrichment (Lmo4, Gpr68 and Siat7e). Figure 1 illustrates the expression levels of the 65 genes in all cortical samples, of which 30 were enriched in FMCx, 24 in TCx and 11 in OCx (Table 2). Gene expression profiles of selected genes are presented in Figure 2 (FMCx), Figure 3 (TCx) and Figure 4 (OCx), whereas the complete gene sets are provided as Additional file 2 (AB1700 data) and Additional file 3 (Illumina data). Fold differences ranged between 1.4 and 13.9. As can be seen from Figures 2, 3 and 4 and Additional file 2, gene expression levels vary within samples from the same cortical region. Such variation within a group is quite common in gene expression studies of animal tissue and is one of the reasons why SAM is preferred over traditional statistical methods such as Student t-test and ANOVA when analysing microarray data. The entire list of regionally enriched genes, including probe and gene identifiers for both microarray platforms and observed fold differences is provided in Additional file 4.


Gene expression in the rat brain: high similarity but unique differences between frontomedial-, temporal- and occipital cortex.

Stansberg C, Ersland KM, van der Valk P, Steen VM - BMC Neurosci (2011)

Spatial and time-dependent expression patterns of genes enriched in OCx. Expression profiles for 4 selected genes in rat brain regions, across different stages of the developing cortex, in astrocytes, oligodendrocytes and neurons and in different neuronal subtypes, as well as laminar expression patterns of the regional genes in their corresponding cortical regions. Profiles (a-d) were generated based on microarray data obtained from [20] (a), [10] (b), [28] (c) and [30] (d). Individual samples, including replicates, are placed along the x-axis. The y-axis indicates normalised signal intensities for each gene in each individual sample. Simple profiles are presented for illustration purposes; full profiles with detailed expression levels and sample information are available as additional material. In situ hybridisation images (e) were downloaded from the Allen Mouse Brain Atlas. FMCx, fronto-medial cortex; TCx, temporal cortex; OCx, occipital cortex.; HiF, Hippocampus; Str, Striatum; Cb, cerebellum; Oligo, oligodendrocytes; Astro, astrocytes; Glu, Glutamatergic neurons; GABA, GABAergic neurons; CgCx, cingulated cortex; SSCx, somatosensory cortex; n.a., not available; * arrows indicate increasingly mature cells
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Figure 4: Spatial and time-dependent expression patterns of genes enriched in OCx. Expression profiles for 4 selected genes in rat brain regions, across different stages of the developing cortex, in astrocytes, oligodendrocytes and neurons and in different neuronal subtypes, as well as laminar expression patterns of the regional genes in their corresponding cortical regions. Profiles (a-d) were generated based on microarray data obtained from [20] (a), [10] (b), [28] (c) and [30] (d). Individual samples, including replicates, are placed along the x-axis. The y-axis indicates normalised signal intensities for each gene in each individual sample. Simple profiles are presented for illustration purposes; full profiles with detailed expression levels and sample information are available as additional material. In situ hybridisation images (e) were downloaded from the Allen Mouse Brain Atlas. FMCx, fronto-medial cortex; TCx, temporal cortex; OCx, occipital cortex.; HiF, Hippocampus; Str, Striatum; Cb, cerebellum; Oligo, oligodendrocytes; Astro, astrocytes; Glu, Glutamatergic neurons; GABA, GABAergic neurons; CgCx, cingulated cortex; SSCx, somatosensory cortex; n.a., not available; * arrows indicate increasingly mature cells
Mentions: After strict manual inspection of all FDR = 0 selected expression profiles, a total of 65 genes were ultimately determined as being markedly enriched in either FMCx, TCx or OCx, of which 54 were supported in both data sets. Nine of the AB1700-generated genes could not be confirmed in the Illumina data, either due to non-representation on the Illumina RatRef-12 array (Aldh3b2, C1ql3, rCG46329, rCG41008, RGD1306921 and Mab21/l) or lack of significant enrichment (Lmo4, Gpr68 and Siat7e). Figure 1 illustrates the expression levels of the 65 genes in all cortical samples, of which 30 were enriched in FMCx, 24 in TCx and 11 in OCx (Table 2). Gene expression profiles of selected genes are presented in Figure 2 (FMCx), Figure 3 (TCx) and Figure 4 (OCx), whereas the complete gene sets are provided as Additional file 2 (AB1700 data) and Additional file 3 (Illumina data). Fold differences ranged between 1.4 and 13.9. As can be seen from Figures 2, 3 and 4 and Additional file 2, gene expression levels vary within samples from the same cortical region. Such variation within a group is quite common in gene expression studies of animal tissue and is one of the reasons why SAM is preferred over traditional statistical methods such as Student t-test and ANOVA when analysing microarray data. The entire list of regionally enriched genes, including probe and gene identifiers for both microarray platforms and observed fold differences is provided in Additional file 4.

Bottom Line: A large proportion of these 65 genes appear to be involved in signal transduction, including the ion channel Fxyd6, the neuropeptide Grp and the nuclear receptor Rorb.We also find that the majority of these genes display increased expression levels around birth and show distinct preferences for certain cortical layers and cell types in rodents.Since specific patterns of expression often are linked to equally specialised biological functions, we propose that these cortex sub-region enriched genes are important for proper functioning of the cortical regions in question.

View Article: PubMed Central - HTML - PubMed

Affiliation: Dr E. Martens Research Group for Biological Psychiatry, Department of Clinical Medicine, University of Bergen, Norway. Christine.Stansberg@uib.no

ABSTRACT

Background: The six-layered neocortex of the mammalian brain may appear largely homologous, but is in reality a modular structure of anatomically and functionally distinct areas. However, global gene expression seems to be almost identical across the cerebral cortex and only a few genes have so far been reported to show regional enrichment in specific cortical areas.

Results: In the present study on adult rat brain, we have corroborated the strikingly similar gene expression among cortical areas. However, differential expression analysis has allowed for the identification of 30, 24 and 11 genes enriched in frontomedial -, temporal- or occipital cortex, respectively. A large proportion of these 65 genes appear to be involved in signal transduction, including the ion channel Fxyd6, the neuropeptide Grp and the nuclear receptor Rorb. We also find that the majority of these genes display increased expression levels around birth and show distinct preferences for certain cortical layers and cell types in rodents.

Conclusions: Since specific patterns of expression often are linked to equally specialised biological functions, we propose that these cortex sub-region enriched genes are important for proper functioning of the cortical regions in question.

Show MeSH
Related in: MedlinePlus