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See detailGlial but not neuronal development in the cochleo-vestibular ganglion requires Sox10.
Breuskin, Ingrid ULg; Bodson, Morgan ULg; Thelen, Nicolas ULg et al

in Journal of Neurochemistry (2010), 114(6), 1827-39

The cochleo-vestibular ganglion contains neural crest-derived glial cells and sensory neurons that are derived from the neurogenic otic placode. Little is known about the molecular mechanisms that ... [more ▼]

The cochleo-vestibular ganglion contains neural crest-derived glial cells and sensory neurons that are derived from the neurogenic otic placode. Little is known about the molecular mechanisms that regulate the tightly orchestrated development of this structure. Here, we report that Sox10, a high-mobility group DNA-binding domain transcription factor that is required for the proper development of neural crest cell derivatives, is specifically expressed in post-migratory neural crest cells in the cochleo-vestibular ganglion. Using Sox10-deficient mice, we demonstrate that this transcription factor is essential for the survival, but not the generation, of the post-migratory neural crest cells within the inner ear. In the absence of these neural crest-derived cells, we have investigated the survival of the otocyst-derived auditory neurons. Surprisingly, auditory neuron differentiation, sensory target innervation and survival are conserved despite the absence of glial cells. Moreover, brain-derived neurotrophic factor expression is increased in the hair cells of Sox10-deficient mice, a compensatory mechanism that may prevent spiral ganglion neuronal cell death. Taken together, these data suggest that in the absence of neural crest-derived glial cells, an increase trophic support from hair cells promotes the survival of spiral ganglion neurons in Sox10 mutant mice. [less ▲]

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See detailHair cell progenitors: identification and regulatory genes
Bodson, Morgan ULg; Breuskin, Ingrid ULg; Lefèbvre, Philippe ULg et al

in Acta Oto-Laryngologica (2009), 10

Hair cell loss in higher vertebrates appears to be permanent. Progenitors that are quiescent in the organ of Corti are the best candidates for the restoration of the different cell types in the organ of ... [more ▼]

Hair cell loss in higher vertebrates appears to be permanent. Progenitors that are quiescent in the organ of Corti are the best candidates for the restoration of the different cell types in the organ of Corti. However, little is known about the presence of these progenitors and their capacity to differentiate into hair cells. This review will first highlight recent findings concerning the identification of progenitor cells that are able to proliferate and to differentiate into hair cells. Principal factors impinging on this process are then reviewed. Auditory hair cell progenitors have been identified and, under appropriate conditions, are capable of proliferating and differentiating into hair cells. Characterization of signals that maintain, expand and regulate these progenitors will be essential for the biomedical application of stem cell populations to restore hearing. [less ▲]

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See detailExpression patterns of miR-96, miR-182 and miR-183 in the development inner ear
Sacheli, Rosalie ULg; Nguyen, Laurent ULg; Borgs, Laurence ULg et al

in Gene Expression Patterns (2009)

MicroRNAs (miRNAs) constitute a class of small non-coding endogenous RNAs that downregulate gene expression by binding to 3' untranslated region (UTR) of target messenger RNAs. Although they have been ... [more ▼]

MicroRNAs (miRNAs) constitute a class of small non-coding endogenous RNAs that downregulate gene expression by binding to 3' untranslated region (UTR) of target messenger RNAs. Although they have been found to regulate developmental and physiological processes in several organs and tissues, their role in the regulation of the inner ear transcriptome remains unknown. In this report, we have performed systematic in situ hybridization to analyze the temporal and spatial distribution of three miRNAs (miR-96, mR-182, and mR-183) that are likely to arise from a single precursor RNA during the development and the maturation of the cochlea. Strikingly we found that the expression of mR-96, mR-182 and mR-183 was highly dynamic during the development of the cochlea, from the patterning to the differentiation of the main cochlear structures. [less ▲]

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See detailSox10 promotes the survival of cochlear progenitors during the establishment of the organ of Corti
Breuskin, Ingrid ULg; Bodson, Morgan ULg; Thelen, Nicolas ULg et al

in Developmental Biology (2009), 15(335), 327-339

Transcription factors of the SoxE family are critical players that underlie various embryological processes. However, little is known about their function during inner ear development. Here, we show that ... [more ▼]

Transcription factors of the SoxE family are critical players that underlie various embryological processes. However, little is known about their function during inner ear development. Here, we show that Sox10 is initially expressed throughout the otic vesicle epithelium and becomes later restricted to supporting cells as cell differentiation proceeds in the organ of Corti. Morphological analyses of Sox10 mutant mice reveal a significant shortening of the cochlear duct likely resulting from the progressive depletion of cochlear progenitors. While Sox10 appears dispensable for the differentiation and patterning of the inner ear prosensory progenitors, our data support a critical role for this transcription factor in the promotion of their survival. We provide genetic evidences that Sox10, in a concentration-dependant manner, could play a role in the regulation of Jagged1, a gene known to be important for inner ear prosensory development. Together, our results demonstrate that Sox10 regulates the biology of early cochlear progenitors during inner ear development, but, in contrast to neural crest-derived cells, this transcription factor is dispensable for their differentiation. Evidence also suggests that this effect occurs via the activation of the Jagged1 gene. [less ▲]

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See detailStrategies to Regenerate Hair Cells: Identification of Progenitors and Critical Genes
Breuskin, Ingrid ULg; Bodson, Morgan ULg; Thelen, Nicolas ULg et al

in Hearing Research (2008), 236(1-2), 1-10

Deafness commonly results from a lesion of the sensory cells and/or of the neurons of the auditory part of the inner ear. There are currently no treatments designed to halt or reverse the progression of ... [more ▼]

Deafness commonly results from a lesion of the sensory cells and/or of the neurons of the auditory part of the inner ear. There are currently no treatments designed to halt or reverse the progression of hearing loss. A key goal in developing therapy for sensorineural deafness is the identification of strategies to replace lost hair cells. In amphibians and birds, a spontaneous post-injury regeneration of all inner ear sensory hair cells occurs. In contrast, in the mammalian cochlea, hair cells are only produced during embryogenesis. Many studies have been carried out in order to demonstrate the persistence of endogenous progenitors. The present review is first focused on the occurrence of spontaneous supernumerary hair cells and on nestin positive precursors found in the organ of Corti. A second approach to regenerating hair cells would be to find genes essential for their differentiation. This review will also focus on critical genes for embryonic hair cell formation such as the cell cycle related proteins, the Atoh1 gene and the Notch signaling pathway. Understanding mechanisms that underlie hair cell production is an essential prerequisite to defining therapeutic strategies to regenerate hair cells in the mature inner ear. [less ▲]

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