Gene expression profiling analysis of the inner ear

Hildebrand, Michael S.; Silva, Michelle G. de; Klockars, Tuomas; Campbell, Colleen A.; Smith, Richard J.H.; Dahl, Hans‐Henrik M.

doi:10.1016/j.heares.2007.01.015

Cited by 10 publications

(10 citation statements)

References 72 publications

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“…These cellular maintenance genes were represented in greater numbers in comparison to genes specific to inner ear function such as IET/Xl-PSIDs and DF/Xl-PSIDs (7.1% and 1.6%, respectively of the 10 th equal tally decile and the IET/Xl-PSIDs, 7.5% of the 10 th equal intensity tally decile). These findings are consistent with observations by other researchers who have noted that genes influential in other tissue types (and not directly related to hair cell mechanotransduction) are highly expressed in the inner ear [23,42,70]. …”

Section: Discussionsupporting

confidence: 93%

“…A list of 681 human orthologues was compiled from inner ear gene expression studies (cDNA library, microarray) of human, mouse, rat, and chicken [22-27,42,85]. Due to differences in inner ear gene designations, we determined the universal gene HGNC symbol that represents each gene by using the UCSC Genome Browser (human NCBI36/hg18 assembly, [86]).…”

Section: Methodsmentioning

confidence: 99%

“…This omission may be partially attributed to the novelty of transcriptional profiling and similar large-scale genetic analyses as tools for uncovering inner ear function in any species [23-28]. Although inner ear genes have been characterized individually in amphibians and other species [36,39-41], large-scale transcriptome analysis has unprecedented potential to significantly advance the field of inner ear genetics [23,27,28,42]. …”

Section: Introductionmentioning

confidence: 99%

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Probing the Xenopus laevis inner ear transcriptome for biological function

et al. 2012

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BackgroundThe senses of hearing and balance depend upon mechanoreception, a process that originates in the inner ear and shares features across species. Amphibians have been widely used for physiological studies of mechanotransduction by sensory hair cells. In contrast, much less is known of the genetic basis of auditory and vestibular function in this class of animals. Among amphibians, the genus Xenopus is a well-characterized genetic and developmental model that offers unique opportunities for inner ear research because of the amphibian capacity for tissue and organ regeneration. For these reasons, we implemented a functional genomics approach as a means to undertake a large-scale analysis of the Xenopus laevis inner ear transcriptome through microarray analysis.ResultsMicroarray analysis uncovered genes within the X. laevis inner ear transcriptome associated with inner ear function and impairment in other organisms, thereby supporting the inclusion of Xenopus in cross-species genetic studies of the inner ear. The use of gene categories (inner ear tissue; deafness; ion channels; ion transporters; transcription factors) facilitated the assignment of functional significance to probe set identifiers. We enhanced the biological relevance of our microarray data by using a variety of curation approaches to increase the annotation of the Affymetrix GeneChip® Xenopus laevis Genome array. In addition, annotation analysis revealed the prevalence of inner ear transcripts represented by probe set identifiers that lack functional characterization.ConclusionsWe identified an abundance of targets for genetic analysis of auditory and vestibular function. The orthologues to human genes with known inner ear function and the highly expressed transcripts that lack annotation are particularly interesting candidates for future analyses. We used informatics approaches to impart biologically relevant information to the Xenopus inner ear transcriptome, thereby addressing the impediment imposed by insufficient gene annotation. These findings heighten the relevance of Xenopus as a model organism for genetic investigations of inner ear organogenesis, morphogenesis, and regeneration.

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Section: Discussionsupporting

confidence: 93%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Probing the Xenopus laevis inner ear transcriptome for biological function

et al. 2012

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“…This is likely due to the difficulty of isolating the different cell types and the tiny amounts of tissue that can be harvested from a single animal. However, this approach has the drawback of diluting the expression data and increasing the complexity of data analysis (Hildebrand et al , 2007). To overcome these obstacles, we genetically labeled ganglia with GFP and then isolated the tissue by careful microdissection or by fluorescence-activated cell sorting (FACS).…”

Section: Resultsmentioning

confidence: 99%

Developmental Profiling of Spiral Ganglion Neurons Reveals Insights into Auditory Circuit Assembly

Appler²,

Houseman³

et al. 2011

Journal of Neuroscience

130

145

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The sense of hearing depends on the faithful transmission of sound information from the ear to the brain by spiral ganglion (SG) neurons. However, how SG neurons develop the connections and properties that underlie auditory processing is largely unknown. We catalogued gene expression in mouse SG neurons from embryonic day 12 (E12), when SG neurons first extend projections, up until postnatal day 15 (P15), after the onset of hearing. For comparison, we also analyzed the closely-related vestibular ganglion (VG). Gene ontology analysis confirmed enriched expression of genes associated with gene regulation and neurite outgrowth at early stages, with the SG and VG often expressing different members of the same gene family. At later stages, the neurons transcribe more genes related to mature function, and exhibit a dramatic increase in immune gene expression. Comparisons of the two populations revealed enhanced expression of TGFβ pathway components in SG neurons and established new markers that consistently distinguish auditory and vestibular neurons. Unexpectedly, we found that Gata3, a transcription factor commonly associated with auditory development, is also expressed in VG neurons at early stages. We therefore defined new cohorts of transcription factors and axon guidance molecules that are uniquely expressed in SG neurons and may drive auditory-specific aspects of their differentiation and wiring. We show that one of these molecules, the receptor guanylyl cyclase Npr2, is required for bifurcation of the SG central axon. Hence, our data set provides a useful resource for uncovering the molecular basis of specific auditory circuit assembly events.

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“…The absolute level of the transcription factors may not be the critical factor as indicated by the existence of transcription modules (Cartharius et al, 2005). Genes do not have to be highly expressed to play regulatory roles (Hildebrand et al, 2007). The exponential regression between Gata-3, -2 and prestin indicate that different prestin levels require a different threshold of Gata-3/-2.…”

Section: Discussionmentioning

confidence: 99%