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-γ 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.
Highlights
The superior olivary complex (SOC) is an essential center for spatial hearing
3 The abbreviations used are: Pn, postnatal day n; SOC, superior olivary complex; MNTB, medial nucleus of the trapezoid body; transcription factors (TFs), transcription factor; Br, brain; oligo, oligonucleotide; qRT-PCR, quantitative RT-PCR; TAHI, transcripts associated with hearing impairment
We randomly picked n genes in the 18,489 genes covered by the Agilent microarray, retrieved their human orthologues, and counted the number of deafness loci covered by at least one orthologue (n corresponds to the number of R. norvegicus genes of the data set of interest)
Summary
The superior olivary complex (SOC) is an essential center for spatial hearing. 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)). 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. 29 of 453 SOC-related oligos mapped within 19 genetic intervals associated with hearing impairment. A prominent center in the mammalian auditory brainstem is the superior olivary complex (SOC). It consists of various nuclei, such as the lateral superior olive, the medial superior
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