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Birdsong "transcriptomics": neurochemical specializations of the oscine song system.

Lovell PV, Clayton DF, Replogle KL, Mello CV - PLoS ONE (2008)

Bottom Line: These markers clearly differentiate HVC from the general pallial region to which HVC belongs, and thus represent molecular specializations of this song nucleus.Our study represents one of the most comprehensive molecular genetic characterizations of a brain nucleus involved in a complex learned behavior in a vertebrate.The data indicate numerous targets for pharmacological and genetic manipulations of the song system, and provide novel insights into mechanisms that might play a role in the regulation of song behavior and/or vocal learning.

View Article: PubMed Central - PubMed

Affiliation: Neurological Sciences Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.

ABSTRACT

Background: Vocal learning is a rare and complex behavioral trait that serves as a basis for the acquisition of human spoken language. In songbirds, vocal learning and production depend on a set of specialized brain nuclei known as the song system.

Methodology/principal findings: Using high-throughput functional genomics we have identified approximately 200 novel molecular markers of adult zebra finch HVC, a key node of the song system. These markers clearly differentiate HVC from the general pallial region to which HVC belongs, and thus represent molecular specializations of this song nucleus. Bioinformatics analysis reveals that several major neuronal cell functions and specific biochemical pathways are the targets of transcriptional regulation in HVC, including: 1) cell-cell and cell-substrate interactions (e.g., cadherin/catenin-mediated adherens junctions, collagen-mediated focal adhesions, and semaphorin-neuropilin/plexin axon guidance pathways); 2) cell excitability (e.g., potassium channel subfamilies, cholinergic and serotonergic receptors, neuropeptides and neuropeptide receptors); 3) signal transduction (e.g., calcium regulatory proteins, regulators of G-protein-related signaling); 4) cell proliferation/death, migration and differentiation (e.g., TGF-beta/BMP and p53 pathways); and 5) regulation of gene expression (candidate retinoid and steroid targets, modulators of chromatin/nucleolar organization). The overall direction of regulation suggest that processes related to cell stability are enhanced, whereas proliferation, growth and plasticity are largely suppressed in adult HVC, consistent with the observation that song in this songbird species is mostly stable in adulthood.

Conclusions/significance: Our study represents one of the most comprehensive molecular genetic characterizations of a brain nucleus involved in a complex learned behavior in a vertebrate. The data indicate numerous targets for pharmacological and genetic manipulations of the song system, and provide novel insights into mechanisms that might play a role in the regulation of song behavior and/or vocal learning.

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Related in: MedlinePlus

AgBase (http://www.agbase.msstate.edu/) was used to assign GO terms (www.geneontology.org) to as many genes as possible from the FDR <0.05 marker list, and to a set of a randomly sampled 1415 ESTIMA Unigenes expressed in zebra finch brain (see text for details).(A and B) Bar graphs show the percentages of genes that were categorized as involved in a specific biological process (A) or activity (B) that minimally describes 3% of the genes in ESTIMA (Grey columns) or in the FDR<0.05 marker lists (Black columns). For each category, black columns with higher or lower percentages than the corresponding grey column are considered over- and under-represented in HVC, respectively. Because some genes are represented by more than one category, percentages in both graphs sum to more than 100%.
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pone-0003440-g004: AgBase (http://www.agbase.msstate.edu/) was used to assign GO terms (www.geneontology.org) to as many genes as possible from the FDR <0.05 marker list, and to a set of a randomly sampled 1415 ESTIMA Unigenes expressed in zebra finch brain (see text for details).(A and B) Bar graphs show the percentages of genes that were categorized as involved in a specific biological process (A) or activity (B) that minimally describes 3% of the genes in ESTIMA (Grey columns) or in the FDR<0.05 marker lists (Black columns). For each category, black columns with higher or lower percentages than the corresponding grey column are considered over- and under-represented in HVC, respectively. Because some genes are represented by more than one category, percentages in both graphs sum to more than 100%.

Mentions: We used GO analysis to identify biological processes and/or molecular functions that are over- or under-represented among HVC regulated genes (i.e., those differentially expressed between HVC and Shelf) as compared to a larger list representing a broader universe of genes expressed in the songbird brain (i.e. a subset of the ESTIMA collection of brain-expressed genes). Because GO comparisons do not take into account the magnitude or direction of gene regulation (up or down), all HVC markers were included in the analysis. Several GO categories were over-represented among HVC markers, including signal transduction, ion transport, and synaptic transmission (Fig. 4A). Accordingly, >40% of the products of HVC markers (as compared to 21% for the broader brain collection) localize to the plasma membrane, and a majority have receptor, ion channel, calcium ion binding, and G-protein signaling activities (Fig. 4B). Genes involved in cell adhesion (Fig. 4A), including several with actin-binding and structural molecule activity (Fig. 4B) were also over-represented. In contrast, genes primarily localized to the nucleus, including genes with DNA binding and transcriptional activity (Fig. 4B) were under-represented. General biochemical processes such as proteolysis, phosphorylation, and hydrolysis had large numbers of hits, comparable to the general brain sample.


Birdsong "transcriptomics": neurochemical specializations of the oscine song system.

Lovell PV, Clayton DF, Replogle KL, Mello CV - PLoS ONE (2008)

AgBase (http://www.agbase.msstate.edu/) was used to assign GO terms (www.geneontology.org) to as many genes as possible from the FDR <0.05 marker list, and to a set of a randomly sampled 1415 ESTIMA Unigenes expressed in zebra finch brain (see text for details).(A and B) Bar graphs show the percentages of genes that were categorized as involved in a specific biological process (A) or activity (B) that minimally describes 3% of the genes in ESTIMA (Grey columns) or in the FDR<0.05 marker lists (Black columns). For each category, black columns with higher or lower percentages than the corresponding grey column are considered over- and under-represented in HVC, respectively. Because some genes are represented by more than one category, percentages in both graphs sum to more than 100%.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2563692&req=5

pone-0003440-g004: AgBase (http://www.agbase.msstate.edu/) was used to assign GO terms (www.geneontology.org) to as many genes as possible from the FDR <0.05 marker list, and to a set of a randomly sampled 1415 ESTIMA Unigenes expressed in zebra finch brain (see text for details).(A and B) Bar graphs show the percentages of genes that were categorized as involved in a specific biological process (A) or activity (B) that minimally describes 3% of the genes in ESTIMA (Grey columns) or in the FDR<0.05 marker lists (Black columns). For each category, black columns with higher or lower percentages than the corresponding grey column are considered over- and under-represented in HVC, respectively. Because some genes are represented by more than one category, percentages in both graphs sum to more than 100%.
Mentions: We used GO analysis to identify biological processes and/or molecular functions that are over- or under-represented among HVC regulated genes (i.e., those differentially expressed between HVC and Shelf) as compared to a larger list representing a broader universe of genes expressed in the songbird brain (i.e. a subset of the ESTIMA collection of brain-expressed genes). Because GO comparisons do not take into account the magnitude or direction of gene regulation (up or down), all HVC markers were included in the analysis. Several GO categories were over-represented among HVC markers, including signal transduction, ion transport, and synaptic transmission (Fig. 4A). Accordingly, >40% of the products of HVC markers (as compared to 21% for the broader brain collection) localize to the plasma membrane, and a majority have receptor, ion channel, calcium ion binding, and G-protein signaling activities (Fig. 4B). Genes involved in cell adhesion (Fig. 4A), including several with actin-binding and structural molecule activity (Fig. 4B) were also over-represented. In contrast, genes primarily localized to the nucleus, including genes with DNA binding and transcriptional activity (Fig. 4B) were under-represented. General biochemical processes such as proteolysis, phosphorylation, and hydrolysis had large numbers of hits, comparable to the general brain sample.

Bottom Line: These markers clearly differentiate HVC from the general pallial region to which HVC belongs, and thus represent molecular specializations of this song nucleus.Our study represents one of the most comprehensive molecular genetic characterizations of a brain nucleus involved in a complex learned behavior in a vertebrate.The data indicate numerous targets for pharmacological and genetic manipulations of the song system, and provide novel insights into mechanisms that might play a role in the regulation of song behavior and/or vocal learning.

View Article: PubMed Central - PubMed

Affiliation: Neurological Sciences Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.

ABSTRACT

Background: Vocal learning is a rare and complex behavioral trait that serves as a basis for the acquisition of human spoken language. In songbirds, vocal learning and production depend on a set of specialized brain nuclei known as the song system.

Methodology/principal findings: Using high-throughput functional genomics we have identified approximately 200 novel molecular markers of adult zebra finch HVC, a key node of the song system. These markers clearly differentiate HVC from the general pallial region to which HVC belongs, and thus represent molecular specializations of this song nucleus. Bioinformatics analysis reveals that several major neuronal cell functions and specific biochemical pathways are the targets of transcriptional regulation in HVC, including: 1) cell-cell and cell-substrate interactions (e.g., cadherin/catenin-mediated adherens junctions, collagen-mediated focal adhesions, and semaphorin-neuropilin/plexin axon guidance pathways); 2) cell excitability (e.g., potassium channel subfamilies, cholinergic and serotonergic receptors, neuropeptides and neuropeptide receptors); 3) signal transduction (e.g., calcium regulatory proteins, regulators of G-protein-related signaling); 4) cell proliferation/death, migration and differentiation (e.g., TGF-beta/BMP and p53 pathways); and 5) regulation of gene expression (candidate retinoid and steroid targets, modulators of chromatin/nucleolar organization). The overall direction of regulation suggest that processes related to cell stability are enhanced, whereas proliferation, growth and plasticity are largely suppressed in adult HVC, consistent with the observation that song in this songbird species is mostly stable in adulthood.

Conclusions/significance: Our study represents one of the most comprehensive molecular genetic characterizations of a brain nucleus involved in a complex learned behavior in a vertebrate. The data indicate numerous targets for pharmacological and genetic manipulations of the song system, and provide novel insights into mechanisms that might play a role in the regulation of song behavior and/or vocal learning.

Show MeSH
Related in: MedlinePlus