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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: 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.Our study represents one of the most comprehensive molecular genetic characterizations of a brain nucleus involved in a complex learned behavior in a vertebrate.

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

Gene abbreviations are in the text and Tables S1 and S3.Rectangles constitute important nodes in the network that have receptor activities, genes presented in ovals play either a regulatory role, or are products of transcription (shown in the nucleus). Not all connections and nodes are included; genes not required for network assembly, or not present on the arrays were omitted for clarity. Rectangular and oval symbols depicted in grey indicate genes from our primary or secondary lists (asterisks), symbols or fractions of symbols shown in white were either not differentially expressed (solid) or not on our array (dashed). Major cellular compartments are indicated along the top or by the presence of phospholipid membranes.
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pone-0003440-g008: Gene abbreviations are in the text and Tables S1 and S3.Rectangles constitute important nodes in the network that have receptor activities, genes presented in ovals play either a regulatory role, or are products of transcription (shown in the nucleus). Not all connections and nodes are included; genes not required for network assembly, or not present on the arrays were omitted for clarity. Rectangular and oval symbols depicted in grey indicate genes from our primary or secondary lists (asterisks), symbols or fractions of symbols shown in white were either not differentially expressed (solid) or not on our array (dashed). Major cellular compartments are indicated along the top or by the presence of phospholipid membranes.

Mentions: The dynamics of cell proliferation, migration, differentiation and survival play prominent roles in shaping the anatomical and functional organization of HVC throughout life. Accordingly, nearly 25% of our HVC markers were linked to these processes, including a large cluster of non-p53 related genes involved in cell proliferation and cycle progression that were enriched in HVC, and a set of genes related to tumor suppression and/or proliferation that had low HVC expression (Table 5). A second large cluster was related to TGF-beta (Fig. 8), suggesting that this signaling pathway is a major target of regulation in HVC. Finally, a third cluster has been specifically linked to apoptosis and/or p53 tumor-suppressor function. The low HVC expression of several key apoptosis mediators suggests a general downregulation of apoptosis-related signaling, perhaps favoring increased cell survival. Overall, our data suggest that pathways related to cell growth and proliferation may be largely suppressed in HVC, while those involved in promoting cell survival may be active. These conclusions are consistent with the notion that song in this songbird species is highly stable in adulthood. We suggest that these pathways could be more active during the learning period, when the song system undergoes marked changes in its composition and size. A further test of this correlation will be to investigate the expression of these HVC markers in birds that show fluctuations in song production patterns during adulthood. It is possible that proliferation-related markers localize to the ventricular zone dorsal to HVC, a possible source of newly-formed neurons in HVC that was most likely included in our dissected samples. Alternatively, these markers may relate to the proliferative control of glial and/or endothelial cells. Studies of cellular expression in birds of different ages during song development will be essential to clarify the significance of regulating these pathways in HVC.


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

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

Gene abbreviations are in the text and Tables S1 and S3.Rectangles constitute important nodes in the network that have receptor activities, genes presented in ovals play either a regulatory role, or are products of transcription (shown in the nucleus). Not all connections and nodes are included; genes not required for network assembly, or not present on the arrays were omitted for clarity. Rectangular and oval symbols depicted in grey indicate genes from our primary or secondary lists (asterisks), symbols or fractions of symbols shown in white were either not differentially expressed (solid) or not on our array (dashed). Major cellular compartments are indicated along the top or by the presence of phospholipid membranes.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0003440-g008: Gene abbreviations are in the text and Tables S1 and S3.Rectangles constitute important nodes in the network that have receptor activities, genes presented in ovals play either a regulatory role, or are products of transcription (shown in the nucleus). Not all connections and nodes are included; genes not required for network assembly, or not present on the arrays were omitted for clarity. Rectangular and oval symbols depicted in grey indicate genes from our primary or secondary lists (asterisks), symbols or fractions of symbols shown in white were either not differentially expressed (solid) or not on our array (dashed). Major cellular compartments are indicated along the top or by the presence of phospholipid membranes.
Mentions: The dynamics of cell proliferation, migration, differentiation and survival play prominent roles in shaping the anatomical and functional organization of HVC throughout life. Accordingly, nearly 25% of our HVC markers were linked to these processes, including a large cluster of non-p53 related genes involved in cell proliferation and cycle progression that were enriched in HVC, and a set of genes related to tumor suppression and/or proliferation that had low HVC expression (Table 5). A second large cluster was related to TGF-beta (Fig. 8), suggesting that this signaling pathway is a major target of regulation in HVC. Finally, a third cluster has been specifically linked to apoptosis and/or p53 tumor-suppressor function. The low HVC expression of several key apoptosis mediators suggests a general downregulation of apoptosis-related signaling, perhaps favoring increased cell survival. Overall, our data suggest that pathways related to cell growth and proliferation may be largely suppressed in HVC, while those involved in promoting cell survival may be active. These conclusions are consistent with the notion that song in this songbird species is highly stable in adulthood. We suggest that these pathways could be more active during the learning period, when the song system undergoes marked changes in its composition and size. A further test of this correlation will be to investigate the expression of these HVC markers in birds that show fluctuations in song production patterns during adulthood. It is possible that proliferation-related markers localize to the ventricular zone dorsal to HVC, a possible source of newly-formed neurons in HVC that was most likely included in our dissected samples. Alternatively, these markers may relate to the proliferative control of glial and/or endothelial cells. Studies of cellular expression in birds of different ages during song development will be essential to clarify the significance of regulating these pathways in HVC.

Bottom Line: 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.Our study represents one of the most comprehensive molecular genetic characterizations of a brain nucleus involved in a complex learned behavior in a vertebrate.

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