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dc.contributor.authorHackett, Troy A.en_US
dc.contributor.authorGuo, Yanen_US
dc.contributor.authorClause, Amandaen_US
dc.contributor.authorHackett, Nicholas J.en_US
dc.contributor.authorGarbett, Krassimiraen_US
dc.contributor.authorZhang, Panen_US
dc.contributor.authorPolley, Daniel B.en_US
dc.contributor.authorMirnics, Karolyen_US
dc.date.accessioned2015-09-01T13:28:23Z
dc.date.issued2015en_US
dc.identifier.citationHackett, Troy A., Yan Guo, Amanda Clause, Nicholas J. Hackett, Krassimira Garbett, Pan Zhang, Daniel B. Polley, and Karoly Mirnics. 2015. “Transcriptional maturation of the mouse auditory forebrain.” BMC Genomics 16 (1): 606. doi:10.1186/s12864-015-1709-8. http://dx.doi.org/10.1186/s12864-015-1709-8.en
dc.identifier.issn1471-2164en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:21462360
dc.description.abstractBackground: The maturation of the brain involves the coordinated expression of thousands of genes, proteins and regulatory elements over time. In sensory pathways, gene expression profiles are modified by age and sensory experience in a manner that differs between brain regions and cell types. In the auditory system of altricial animals, neuronal activity increases markedly after the opening of the ear canals, initiating events that culminate in the maturation of auditory circuitry in the brain. This window provides a unique opportunity to study how gene expression patterns are modified by the onset of sensory experience through maturity. As a tool for capturing these features, next-generation sequencing of total RNA (RNAseq) has tremendous utility, because the entire transcriptome can be screened to index expression of any gene. To date, whole transcriptome profiles have not been generated for any central auditory structure in any species at any age. In the present study, RNAseq was used to profile two regions of the mouse auditory forebrain (A1, primary auditory cortex; MG, medial geniculate) at key stages of postnatal development (P7, P14, P21, adult) before and after the onset of hearing (~P12). Hierarchical clustering, differential expression, and functional geneset enrichment analyses (GSEA) were used to profile the expression patterns of all genes. Selected genesets related to neurotransmission, developmental plasticity, critical periods and brain structure were highlighted. An accessible repository of the entire dataset was also constructed that permits extraction and screening of all data from the global through single-gene levels. To our knowledge, this is the first whole transcriptome sequencing study of the forebrain of any mammalian sensory system. Although the data are most relevant for the auditory system, they are generally applicable to forebrain structures in the visual and somatosensory systems, as well. Results: The main findings were: (1) Global gene expression patterns were tightly clustered by postnatal age and brain region; (2) comparing A1 and MG, the total numbers of differentially expressed genes were comparable from P7 to P21, then dropped to nearly half by adulthood; (3) comparing successive age groups, the greatest numbers of differentially expressed genes were found between P7 and P14 in both regions, followed by a steady decline in numbers with age; (4) maturational trajectories in expression levels varied at the single gene level (increasing, decreasing, static, other); (5) between regions, the profiles of single genes were often asymmetric; (6) GSEA revealed that genesets related to neural activity and plasticity were typically upregulated from P7 to adult, while those related to structure tended to be downregulated; (7) GSEA and pathways analysis of selected functional networks were not predictive of expression patterns in the auditory forebrain for all genes, reflecting regional specificity at the single gene level. Conclusions: Gene expression in the auditory forebrain during postnatal development is in constant flux and becomes increasingly stable with age. Maturational changes are evident at the global through single gene levels. Transcriptome profiles in A1 and MG are distinct at all ages, and differ from other brain regions. The database generated by this study provides a rich foundation for the identification of novel developmental biomarkers, functional gene pathways, and targeted studies of postnatal maturation in the auditory forebrain. Electronic supplementary material The online version of this article (doi:10.1186/s12864-015-1709-8) contains supplementary material, which is available to authorized users.en
dc.language.isoen_USen
dc.publisherBioMed Centralen
dc.relation.isversionofdoi:10.1186/s12864-015-1709-8en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536593/pdf/en
dash.licenseLAAen_US
dc.subjectSynapseen
dc.subjectPlasticityen
dc.subjectDevelopmenten
dc.subjectCritical perioden
dc.subjectCortexen
dc.subjectThalamusen
dc.subjectNeurotransmissionen
dc.subjectNeuromodulationen
dc.subjectExtracellular matrixen
dc.subjectMyelinationen
dc.subjectRNAseqen
dc.subjectPathway analysisen
dc.subjectSequencingen
dc.subjectRNAen
dc.titleTranscriptional maturation of the mouse auditory forebrainen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalBMC Genomicsen
dash.depositing.authorClause, Amandaen_US
dc.date.available2015-09-01T13:28:23Z
dc.identifier.doi10.1186/s12864-015-1709-8*
dash.authorsorderedfalse
dash.contributor.affiliatedClause, Amanda
dash.contributor.affiliatedPolley, Daniel


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