Expression and Function of Sox21 During Mouse Cochlea Development

Abstract

The development of the inner ear is an orchestrated process of morphogenesis with spatiotemporally controlled generations of individual cell types. Recent studies have revealed that the Sox gene family, a family of evolutionarily conserved HMG-type transcriptional factors, is differentially expressed in each cell type of the mammalian inner ear and plays critical roles in cell-fate determination during development. In this study, we examined the expression pattern of Sox21 in the developing and adult murine cochlea. Sox21 was expressed throughout the sensory epithelium in the early otocyst stage but became restricted to supporting cells during adulthood. Interestingly, the expression in adults was restricted to the inner phalangeal, inner border, and Deiters' cells: all of these cells are in direct contact with hair cells. Evaluations of the auditory brainstem-response revealed that Sox21(-/-) mice suffered mild hearing impairments, with an increase in hair cells that miss their appropriate planar cell polarity. Taken together with the previously reported critical roles of SoxB1 families in the morphogenesis of inner ear sensory and neuronal cells, our results suggest that Sox21, a counteracting partner of the SoxB1 family, controls fine-tuned cell fate decisions. Also, the characteristic expression pattern may be useful for labelling a particular subset of supporting cells.

Sox21 regulates the progression of neuronal differentiation in a dose-dependent manner

“…Sox21 function and its role in neurogenesis may also depend on the interaction of different partner proteins based on its level of expression. In addition to its roles in neurogenesis, Sox21 has also been shown to be required for the development of other organs, including sensory epithelium in developing cochlea (inner ear) of mice (Hosoya et al, 2011) and the cuticle layer and the progenitor cells of the hair shaft in both mouse and human (Kiso et al, 2009). Again this suggests that its multiple roles in development may be specified by cooperation with different partners in different environments at different times during development.…”

Inner ear supporting cells: Rethinking the silent majority

“…Aquaporin4 is found in Hensen’s cells [90]. Sox21 is expressed in inner phalangeal cells, inner border cells, and Deiters' cells [91]. Although these genes and several others have been used as markers for different supporting cell populations, their physiological contributions to the functional diversity of supporting cells remain elusive.…”

Recent development of AAV-based gene therapies for inner ear disorders

“…Ocm [64] Gjb2 [30] Syn [65] Slc26a5 [66] Lgr5 [67,68] NeuN [69] Otof [70] GFAP [71] Map2 [72] Atp2a3 [70,73] Fgfr3 [74] Tuj1 [75] Tpbgl [70] Tak1 [76] Calb1 [77] Dnajc5b [70] Sox21 [78] Calb2 [79] Myo7a [80] Sox2 [81,82] Nos1 [83] Myo6 [84] PLP1 [68] Runx1…”