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Time-dependent gene expression analysis of the developing superior olivary complex.

ABSTRACT: The superior olivary complex (SOC) is an essential auditory brainstem relay involved in sound localization. To identify the genetic program underlying its maturation, we profiled the rat SOC transcriptome at postnatal days 0, 4, 16, and 25 (P0, P4, P16, and P25, respectively), using genome-wide microarrays (41,012 oligonucleotides (oligos)). Differences in gene expression between two consecutive stages were highest between P4 and P16 (3.6%) and dropped to 0.06% between P16 and P25. To identify SOC-related genetic programs, we also profiled the entire brain at P4 and P25. The number of differentially expressed oligonucleotides between SOC and brain almost doubled from P4 to P25 (4.4% versus 7.6%). These data demonstrate considerable molecular specification around hearing onset, which is rapidly finalized. Prior to hearing onset, several transcription factors associated with the peripheral auditory system were up-regulated, probably coordinating the development of the auditory system. Additionally, crystallin-? subunits and serotonin-related genes were highly expressed. The molecular repertoire of mature neurons was sculpted by SOC-related up- and down-regulation of voltage-gated channels and G-proteins. Comparison with the brain revealed a significant enrichment of hearing impairment-related oligos in the SOC (26 in the SOC, only 11 in the brain). Furthermore, 29 of 453 SOC-related oligos mapped within 19 genetic intervals associated with hearing impairment. Together, we identified sequential genetic programs in the SOC, thereby pinpointing candidates that may guide its development and ensure proper function. The enrichment of hearing impairment-related genes in the SOC may have implications for restoring hearing because central auditory structures might be more severely affected than previously appreciated.

SUBMITTER: Ehmann H

PROVIDER: S-EPMC3764792 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Time-dependent gene expression analysis of the developing superior olivary complex.

Ehmann Heike H Hartwich Heiner H Salzig Christian C Hartmann Nadja N Clément-Ziza Mathieu M Ushakov Kathy K Avraham Karen B KB Bininda-Emonds Olaf R P ORP Hartmann Alexander K AK Lang Patrick P Friauf Eckhard E Nothwang Hans Gerd HG

The Journal of biological chemistry 20130726 36

The superior olivary complex (SOC) is an essential auditory brainstem relay involved in sound localization. To identify the genetic program underlying its maturation, we profiled the rat SOC transcriptome at postnatal days 0, 4, 16, and 25 (P0, P4, P16, and P25, respectively), using genome-wide microarrays (41,012 oligonucleotides (oligos)). Differences in gene expression between two consecutive stages were highest between P4 and P16 (3.6%) and dropped to 0.06% between P16 and P25. To identify S ...[more]

PMID: 23893414

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Project description:The superior olivary complex (SOC) is an essential auditory brainstem structure involved in sound localization. In order to identify the genetic program underlying its maturation, we profiled the transcriptome of the rat SOC at postnatal days (P)0, P4, P16, and P25, using genome-wide microarrays (41,012 sequences). Differences in gene expression between two consecutive stages were highest between P4 versus P16 (3.6%), but dropped to 0.06% between P16 versus P25. To identify SOC-related genetic programs, we also profiled the brain at P4 and P25. Differentially expressed sequences between SOC and brain almost doubled from P4 (4.4%) to P25 (7.6%). These datademonstrate considerable molecular specification around hearing onset, which is rapidly finalized. Prior to hearing onset, several transcription factors associated with the peripheral auditory system were up-regulated, likely coordinating auditory system development. Additionally, serotonin-related genes and crystalline-gamma subunits were highly expressed. The molecular repertoire of mature neurons was sculpted by SOC-related up- and down-regulation of several protein categories, among which voltage-gated channels and myelination were prominent. Comparison with the brain revealed a significant enrichment of deafness-related oligos in the SOC-related genetic program (26 in the SOC, only 11 in the brain). Furthermore, 29 out of 453 SOC-related oligos mapped within 19 genetic intervals associated with hearing impairment. Together, we identified sequential genetic programs in the SOC, thereby pinpointing candidates which may guide its development and ensure proper function. The enrichment of deafness-related genes in the SOC may have implications for restoring hearing, as central auditory structures might be more severely affected than previously appreciated. This SuperSeries is composed of the SubSeries listed below. The genome wide expression during the postnatal development of the SOC was investigated at four different time points: at postnatal (P) day 0, P4, P16 and P25. Concerning the brain, P4 and P25 were used. Samples were hybridized onto two color platforms. At least 6 up to nine biological replicates per sample were performed.

Project description:The superior olivary complex (SOC) is a prominent auditory brainstem center and represents one of the prime model systems to study the development of sensory circuits. We recently performed genome-wide microarray studies to analyze the SOC-related genetic program at postnatal day (P)4 and P25. Here, we extended this analysis by including two additional time points, P0 and P16. Data sets were validated by qRT-PCR. Statistical analysis were performed for the different developmental time points as well as with for differences between the SOC and our previously analyzed brain samples. This analysis revealed that after hearing-onset (P16 and P25), 918 oligos were up-regulated and 810 oligos down-regulated in the SOC compared to the two prehearing stages (P0 and P4). Of the up-regulated oligos, 530 were significantly higher expressed compared to the brain at P25. Concerning neurotransmission, SOC-related elevation was mainly observed for K+ channels, G-proteins, and myelination-related proteins, whereas Ca2+-related proteins showed a decreased expression. In the pre-hearing period, 47 oligos were up-regulated compared to the brain. Several of them were transcription factors, previously associated with other auditory structures, and might ensure coordinated development of peripheral and central auditory structures. Stage-specific comparison identified distinct genetic programs during development: Circuit formation/refinement at P4; myelination and circuit refinement/consolidation at P16; and neuroprotection at P25. Altogether, our study defines the genetic program of postnatal SOC development and provides strong functional candidates for various developmental processes. The genome wide expression during the postnatal development of the SOC was investigated at two different time points: at postnatal (P) day 0 (before hearing onset) and P16 (after hearing onset). Samples were hybridized onto two color platforms. At least 6 up to nine biological replicates per sample were performed.

Project description:Neuronal activity is energetically costly, but despite its importance, energy production and consumption have been studied in only a few neurone types. Neuroenergetics is of special importance in auditory brainstem nuclei, where neurones exhibit various biophysical adaptations for extraordinary temporal precision and show particularly high firing rates. We have studied the development of energy metabolism in three principal nuclei of the superior olivary complex (SOC) involved in precise binaural processing in the Mongolian gerbil (Meriones unguiculatus). We used immunohistochemistry to quantify metabolic markers for energy consumption (Na(+)/K(+)-ATPase) and production (mitochondria, cytochrome c oxidase activity and glucose transporter 3 (GLUT3)). In addition, we calculated neuronal ATP consumption for different postnatal ages (P0-90) based upon published electrophysiological and morphological data. Our calculations relate neuronal processes to the regeneration of Na(+) gradients perturbed by neuronal firing, and thus to ATP consumption by Na(+)/K(+)-ATPase. The developmental changes of calculated energy consumption closely resemble those of metabolic markers. Both increase before and after hearing onset occurring at P12-13 and reach a plateau thereafter. The increase in Na(+)/K(+)-ATPase and mitochondria precedes the rise in GLUT3 levels and is already substantial before hearing onset, whilst GLUT3 levels are scarcely detectable at this age. Based on these findings we assume that auditory inputs crucially contribute to metabolic maturation. In one nucleus, the medial nucleus of the trapezoid body (MNTB), the initial rise in marker levels and calculated ATP consumption occurs distinctly earlier than in the other nuclei investigated, and is almost completed by hearing onset. Our study shows that the mathematical model used is applicable to brainstem neurones. Energy consumption varies markedly between SOC nuclei with their different neuronal properties. Especially for the medial superior olive (MSO), we propose that temporally precise input integration is energetically more costly than the high firing frequencies typical for all SOC nuclei.

Dataset Information

Time-dependent gene expression analysis of the developing superior olivary complex.

Publications

Time-dependent gene expression analysis of the developing superior olivary complex.

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