En1 directs superior olivary complex neuron positioning, survival, and expression of FoxP1.
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ABSTRACT:
SUBMITTER: Altieri SC
PROVIDER: S-EPMC4688081 | biostudies-literature | 2015 Dec
REPOSITORIES: biostudies-literature
Publications
En1 directs superior olivary complex neuron positioning, survival, and expression of FoxP1.
Altieri Stefanie C SC Jalabi Walid W Zhao Tianna T Romito-DiGiacomo Rita R RR Maricich Stephen M SM
Developmental biology 20151102 1
Little is known about the genetic pathways and transcription factors that control development and maturation of central auditory neurons. En1, a gene expressed by a subset of developing and mature superior olivary complex (SOC) cells, encodes a homeodomain transcription factor important for neuronal development in the midbrain, cerebellum, hindbrain and spinal cord. Using genetic fate-mapping techniques, we show that all En1-lineal cells in the SOC are neurons and that these neurons are glyciner ...[more]
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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.
2013-07-31 | E-GEOD-36470 | biostudies-arrayexpress
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.
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Project description: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.
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Project description:Many areas of the central nervous system are organized into clusters of cell groups, with component cell groups exhibiting diverse but related functions. One such cluster, the superior olivary complex (SOC), is located in the ventral auditory brainstem in mammals. The SOC is an obligatory contact point for most projection neurons of the ventral cochlear nucleus and plays central roles in many aspects of monaural and binaural information processing. Despite their important interrelated functions, little is known about the embryonic origins of SOC nuclei, due in part to a paucity of developmental markers to distinguish individual cell groups. In this report, we present a collection of novel markers for the developing SOC nuclei in mice, including the transcription factors FoxP1, MafB, and Sox2, and the lineage-marking transgenic line En1-Cre. We use these definitive markers to examine the rhombic lip and rhombomeric origins of SOC nuclei and demonstrate that they can serve to uniquely identify SOC nuclei and subnuclei in newborn pups. The markers are also useful in identifying distinct nuclear domains within the presumptive SOC as early as embryonic day (E) 14.5, well before morphological distinction of individual nuclei is evident. These findings indicate that the mediolateral and dorsoventral position of SOC nuclei characteristic of the adult brainstem is established during early neurogenesis.
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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.
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