Weighted gene co-expression network analysis on microarray data from subregions of zebra finch (Taeniopygia guttata) basal ganglia
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ABSTRACT:
ORGANISM(S): Taeniopygia guttata
PROVIDER: GSE34819 | GEO | 2012/01/04
SECONDARY ACCESSION(S): PRJNA150249
REPOSITORIES: GEO
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Project description:Similarities between speech and birdsong make songbirds advantageous for investigating the neurogenetics of learned vocal communication; a complex phenotype likely supported by ensembles of interacting genes in cortico-basal ganglia pathways of both species. To date, only FoxP2 has been identified as critical to both speech and birdsong. We performed weighted gene co-expression network analysis on microarray data from singing zebra finches to discover gene ensembles regulated during vocal behavior. We found ~2,000 singing- regulated genes comprising 3 co-expression groups unique to area X, the basal ganglia subregion dedicated to learned vocal-motor behavior. These contained known targets of human FOXP2 and potential avian targets. We validated novel biological pathways for vocalization. Our findings show that higher-order gene co-expression patterns, rather than expression levels, molecularly distinguish area X from the ventral striato-pallidum during singing. The previously unknown structure of singing-driven networks enables prioritization of molecular interactors that likely bear on human motor disorders, especially those affecting speech. Gene expression was measured in 2 basal ganglia sub-regions (area X & ventral striato-pallidum (VSP)) of 27 adult male zebra finches that sang different amounts of song over a 2hr period in the morning. 18 birds were allowed to sing freely, 9 birds were discouraged from singing by the presence of an investigator and those that sang fewer than 10 song motifs were considered “non-singers”.
2012-01-04 | E-GEOD-34819 | biostudies-arrayexpress
Project description:Production of learned vocalizations requires precise selection and accurate sequencing of appropriate vocal-motor actions. The basal ganglia are essential for the selection and sequencing of motor actions, but the cellular specializations and circuit mechanisms governing accurate sequencing of vocalizations are unknown. Here, we use single-nucleus RNA sequencing and genetic manipulations to map basal ganglia cell types and circuits involved in the production of songbird vocal sequences. We identify cell-type specializations in direct-like and indirect-like basal ganglia pathways, including evolutionary expansion of striatal and arkypallidal cell-types that could facilitate vocal sequencing. We also reversibly reduced the expression of FoxP2 with a viral knockdown. For birds in which FoxP2 was knocked down, striatal neurons exhibited decreased expression of Drd1 and showed an increased ratio of Drd2/Drd1 expression. These findings identify key evolutionary specializations and circuits essential for selection and sequencing of vocal-motor actions necessary for vocal communication.
2021-05-19 | GSE136086 | GEO
Project description:Human speech is one of the few examples of vocal learning among mammals, yet ~half of avian species exhibit this ability. Its genetic basis is unknown beyond a shared requirement for FoxP2 in both humans and zebra finches. Here we manipulated FoxP2 isoforms in Area X during a critical period for song development, delineating, for the first time, unique contributions of each to vocal learning. We used weighted gene coexpression network analysis of RNA-seq data to construct transcriptional profiles and found gene modules correlated to singing, learning, or vocal variability. The juvenile song modules were preserved adults, whereas the learning modules were not. The learning modules were preserved in the striatopallidum adjacent to Area X whereas the song modules were not. The confluence of learning and singing coexpression in juvenile, but not adult, Area X may underscore molecular processes that drive vocal learning in zebra finches and, by analogy, humans.
2018-01-25 | GSE96843 | GEO
Project description:This study was part of a larger study on the zebra finch genome (Warren et al 2010. Nature). Here we present a summary of the specific experiment on singing-regulated gene expression. To evaluate the genomic landscape of learned vocal communication, we profiled gene expression in the zebra finch song nucleus, Area X, with custom Agilent oligoarrays for up to seven hours following initiation of singing. We developed algorithms to identify singing-regulated transcripts related to time spent singing, and discovered over 800 transcripts in Area X that are significantly regulated by singing. These included known increases of the egr1 and c-fos transcription factors, and a decrease in the FoxP2 transcription factor, a gene associated with spoken language development. We clusted the singing-regulated genes in Area X into 20 temporal dynamic expression patterns, which include rapidly up-regulated and transient, rapidly up-regulated and sustained, slowly up-regulated and sustained, a late upregulated response, and equally diverse clusters of down-regulated patterns. Using promotor motif search algorithms, we found significant over-representation of transcription factor binding sites in the promoters of genes within specific clusters. These binding sites included those of transcription factors known to be activated by neural activity and plasticity, such as CREB, SRF, AP-1, NFKB1, CFOS, EGR1, and MEF2. Gene expression in Area X was measured before singing (0) or after singing for 0.5, 1, 2, 3, 4, 5, 6, and 7hours. Six independent experiments were performed at each of the 9 timepoints.
2010-05-15 | E-GEOD-19900 | biostudies-arrayexpress
Project description:It has been proposed that two amino acid substitutions in the transcription factor FOXP2 have been positively selected during human evolution due to effects on aspects of speech and language. Here, we introduce these substitutions into the endogenous Foxp2 gene.of mice. Although these mice are generally healthy, they have qualitatively different ultrasonic vocalizations, decreased exploratory behavior and decreased dopamine concentrations in the brain suggesting an effect of the humanized Foxp2 allele on basal ganglia. In the striatum, a part of the basal ganglia that is affected in humans with a speech deficit due to one non-functional FOXP2 allele, we find that medium spiny neurons have increased dendrite lengths and increased synaptic plasticity. Since mice carrying one non-functional Foxp2 allele show opposite effects, this suggests that alterations in cortico-basal ganglia circuits might have been important for the evolution of speech and language in humans. In this particular experiment, we investigate the effects of human Foxp2 (Foxp2hum) and the non-functional Foxp2 allele on striatal gene expression in embryonic, young and adult mice. We determined genome-wide gene expression patterns in striatal biopsies from Foxp2hum/hum, Foxp2wt/ko and Foxp2wt/wt mice using high-density oligonucleotide arrays. The animals were derived from two independent FoxP2 knock-in strains and one knock-out strain. In total 71 animals were used, 29 males and 42 females. The mice ages were E16.5, P15, P18, P21 and P95 when sacrificed. The microarrays were processed in totally six batches.
2010-05-22 | E-GEOD-13588 | biostudies-arrayexpress
Project description:Like human speech, birdsong is a complex vocal behavior that is acquired by sensorimotor learning based on coordination of auditory input and vocal output to mimic memorized tutor song. Here we investigate neural circuits for vocal learning and production in deafened songbirds to elucidate how sensory-input regulate genetic and epigenetic property of vocal development and its associated gene expression dynamics. Compared with audition-intact birds, in deafened zebra finches, the vocal development is delayed but song crystallization is observed at more than three times later, producing individually different but structured vocal patterns. In contrast to the distinct difference of vocal ontogeny between audition (+) and (-), unexpectedly, developmental regulation of gene expression dynamics is strictly conserved with age-locked trend in vocal motor circuit in both intact and deafened birds, indicating sensory-input independent robustness of developmental gene expression dynamics in the motor circuit for sensorimotor learning. This discrepancy between outward vocal phenotype and inward gene expression dynamics provides new insight into neural regulation at closing of the critical period for vocal learning by two different forms: auditory inputs-dependent ‘active’ crystallization and gene expression dynamics-mediated ‘passive’ crystallization.
2014-03-21 | GSE56075 | GEO
Project description:Like human speech, birdsong is a complex vocal behavior that is acquired by sensorimotor learning based on coordination of auditory input and vocal output to mimic memorized tutor song. Here we investigate neural circuits for vocal learning and production in deafened songbirds to elucidate how sensory-input regulate genetic and epigenetic property of vocal development and its associated gene expression dynamics. Compared with audition-intact birds, in deafened zebra finches, the vocal development is delayed but song crystallization is observed at more than three times later, producing individually different but structured vocal patterns. In contrast to the distinct difference of vocal ontogeny between audition (+) and (-), unexpectedly, developmental regulation of gene expression dynamics is strictly conserved with age-locked trend in vocal motor circuit in both intact and deafened birds, indicating sensory-input independent robustness of developmental gene expression dynamics in the motor circuit for sensorimotor learning. This discrepancy between outward vocal phenotype and inward gene expression dynamics provides new insight into neural regulation at closing of the critical period for vocal learning by two different forms: auditory inputs-dependent M-bM-^@M-^XactiveM-bM-^@M-^Y crystallization and gene expression dynamics-mediated M-bM-^@M-^XpassiveM-bM-^@M-^Y crystallization. We collected brain samples from intact and early-deafened birds (deafened at day-post hatch 17-23) under silent and dark condition. Song nuclei in vocal motor circuit, HVC and RA tissue samples (juvenile; n = 3, young; n = 3, old; n = 3 of intact and early-deafened birds for HVC and RA) were laser-microdissected from total 24 birds (intact; n = 12, early-deafened; n = 12). Each sample was hybridized to a single array, totaling 36 arrays. Birds were selected per slide such that early-deafened birds were paired with intact birds. To minimize possible interslide bias or batch effects, intact and early-deafened bird samples matching with brain area and age conditions were hybridized side by side on same array glass.
2014-03-21 | E-GEOD-56075 | biostudies-arrayexpress
Project description:It has been proposed that two amino acid substitutions in the transcription factor FOXP2 have been positively selected during human evolution due to effects on aspects of speech and language. Here, we introduce these substitutions into the endogenous Foxp2 gene.of mice. Although these mice are generally healthy, they have qualitatively different ultrasonic vocalizations, decreased exploratory behavior and decreased dopamine concentrations in the brain suggesting an effect of the humanized Foxp2 allele on basal ganglia. In the striatum, a part of the basal ganglia that is affected in humans with a speech deficit due to one non-functional FOXP2 allele, we find that medium spiny neurons have increased dendrite lengths and increased synaptic plasticity. Since mice carrying one non-functional Foxp2 allele show opposite effects, this suggests that alterations in cortico-basal ganglia circuits might have been important for the evolution of speech and language in humans. In this particular experiment, we investigate the effects of human Foxp2 (Foxp2hum) and the non-functional Foxp2 allele on striatal gene expression in embryonic, young and adult mice.
2009-03-02 | GSE13588 | GEO
Project description:This study was part of a larger study on the zebra finch genome (Warren et al 2010. Nature). Here we present a summary of the specific experiment on singing-regulated gene expression. To evaluate the genomic landscape of learned vocal communication, we profiled gene expression in the zebra finch song nucleus, Area X, with custom Agilent oligoarrays for up to seven hours following initiation of singing. We developed algorithms to identify singing-regulated transcripts related to time spent singing, and discovered over 800 transcripts in Area X that are significantly regulated by singing. These included known increases of the egr1 and c-fos transcription factors, and a decrease in the FoxP2 transcription factor, a gene associated with spoken language development. We clusted the singing-regulated genes in Area X into 20 temporal dynamic expression patterns, which include rapidly up-regulated and transient, rapidly up-regulated and sustained, slowly up-regulated and sustained, a late upregulated response, and equally diverse clusters of down-regulated patterns. Using promotor motif search algorithms, we found significant over-representation of transcription factor binding sites in the promoters of genes within specific clusters. These binding sites included those of transcription factors known to be activated by neural activity and plasticity, such as CREB, SRF, AP-1, NFKB1, CFOS, EGR1, and MEF2.
2010-01-16 | GSE19900 | GEO
Project description:Mutations in FOXP2, a member of the forkhead family of transcription factors, are the only known cause of developmental speech and language disorders in humans. To date, there are no known targets of human FOXP2 in the nervous system. The identification of FOXP2 targets in the developing human brain therefore provides a unique tool with which to explore the development of human language and speech. Here we define FOXP2 targets in human basal ganglia (BG) and inferior frontal cortex (IFC) utilizing chromatin immunoprecipitation followed by microarray analysis (ChIP-chip) and validate the functional regulation of targets in vitro. ChIP-chip identified 285 FOXP2 targets in fetal human brain; significant overlap of targets in BG and IFC, indicate a core set of 34 transcriptional targets of FOXP2. We identified targets specific to the IFC or BG, not observed in lung, suggesting important regional and tissue differences in FOXP2 activity. Many target genes are known to play critical roles in specific aspects of CNS patterning or development, such as neurite outgrowth, as well as plasticity. Subsets of the FOXP2 transcriptional targets are either under positive selection in humans, or differentially expressed between human and chimpanzee brain. This is the first ChIP-chip study using human brain tissue, making the FOXP2 target genes identified in these studies important to understanding the pathways regulating speech and language in the developing human brain. These data provide the first insight into the functional network of genes directly regulated by FOXP2 in human brain and by evolutionary comparisons, highlight genes likely to be involved in the development of human higher order cognitive processes. Keywords: ChIP-chip
2007-12-31 | GSE8547 | GEO