Sox10 promotes the survival of cochlear progenitors during the establishment of the organ of Corti

Abstract

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.

De novo SOX10 nonsense mutation in a patient with Kallmann syndrome and hearing loss

“…Our patient also reported early graying of hair, and one patient with KS in Pingault's series had premature whitening of hair (2). Accordingly, SOX10 is important for the development of melanocytes, structures of inner ear, enteric ganglia neurons, Schwann cells, and oligodendrocytes (9,10). Studies with SOX10-null mutant mice show that underlying mechanism of this form of KS results from defects in embryonic development of olfactory ensheathing cells that are required for gonadotropin-releasing hormone neuron migration (2,11).…”

Spectrum of Temporal Bone Abnormalities in Patients with Waardenburg Syndrome andSOX10Mutations

“…SOX10 has been shown to promote the survival of cochlear progenitors during otocyst formation and the establishment of the organ of Corti. 30 It is also expressed persistently in the cochleovestibular ganglia and plays a role in glial development. [30][31][32][33][34] In Sox10 homozygous mutant mice, the differentiation and cellular organization of the organ of Corti and the vestibule appear normal.…”

“…However, the cochlear duct is shortened. 30 In humans, where SOX10 mutations are heterozygous, vestibular abnormalities are much more apparent than those in mice. Other differences have been observed across species: In Sox10 mutant zebrafish, the otic vesicle is smaller or distended, semicircular canals have a delayed development and are thinner than normal, and the sensory epithelia are incorrectly patterned.…”

Review and update of mutations causing Waardenburg syndrome

“…A lack of strial intermediate cells leads to degeneration of the organ of Corti, and thus hearing loss, in several animal models [Tachibana et al, 2003]. However, early and wide SOX10 expression during the inner ear development [Breuskin et al, 2009;Dutton et al, 2009;Watanabe et al, 2000] suggests that other mechanisms may account for deafness associated with SOX10 mutations. A shortening of the cochlea due to a reduced sensory progenitor survival has recently been described in the Sox10 knock-out mouse [Breuskin et al, 2009].…”