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Time course expression study in the rat superior olivary complex

ABSTRACT: 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.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE34003 | GEO | 2013/07/31

SECONDARY ACCESSION(S): PRJNA156453

REPOSITORIES: GEO

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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: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:Spiral ganglion neurons (SGNs) and the associated components of the auditory nerve are primary carriers of auditory information from hair cells to the brain. Loss of SGNs occurs with many pathological conditions, resulting in permanent sensorineural hearing loss. Neural stem/progenitors (NSPs) have been well-characterized in several locations of adult brain and retina. However, it is unclear whether NSPs are present in the adult auditory nerve. Here we examined the self-renewal potential of the adult auditory nerve using ouabain application as a well-established mouse model of acute SGN injury. The observed increase in cell proliferation, alteration in enchromatin/heterochromatin ratio and down-regulation of histone deacetylase expression in glial cells suggest that the quiescent glial cells convert to an activated state after SGN degeneration. This was further confirmed by global gene expression analysis of injured auditory nerves, which showed up-regulation of numerous neurogenesis- and/or development-associated genes shortly after ouabain exposure. These genes include molecular markers commonly used for the identification of NSPs. Under a strict culture regimen, auditory nerve-derived cells of adult mouse ears gave rise to neurospheres, suggesting that multipotent NSPs are present in adult cochlear nerve. Neurosphere assays on Sox2 transgenic mice revealed that Sox2+ glial cells are the source for NSPs. Our data also showed that acute injury or hypoxia enhances neurosphere formation. Taken together, our study revealed that glial cells of adult cochlea exhibit several NSP characteristics, and hence these mature non-neuronal cells may be important targets for promoting self-repair of degenerative auditory nerves. Analysis was conducted on auditory nerve samples from stages encompassing maturation and onset of hearing. Cochleas were collected from euthanized mice (CBA/CaJ) at perinatal (P) stages P0, P3, P7, P10, P14 and P21. Cochleas underwent microdissection to remove the outer bony cochlear shell and cochlear lateral wall, thus preserving the modiolus portion of cochlea which contains mainly the auditory nerve. Paired cochleas (i.e., from left and right ears) from each mouse were pooled to make individual samples. All sample types were done in experimental duplicate (n=2).

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Time course expression study in the rat superior olivary complex

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