Abstract
We investigated DAB1-protein deficiency in the inner-ear development of yotari in comparison to humans and wild-type (wt) mice by immunofluorescence for the expression of connexins (Cxs) and the pannexin Panx1. The spatial and temporal dynamics of Cx26, Cx32, Cx37, Cx40, Cx43, Cx45, and Panx1 were determined in the sixth and eighth weeks of human development and at the corresponding mouse embryonic E13.5 and E15.5, in order to examine gap junction intercellular communication (GJIC) and hemichannel formation. The quantification of the area percentage covered by positive signal was performed for the epithelium and mesenchyme of the cochlear and semicircular ducts and is expressed as the mean ± SD. The data were analysed by one-way ANOVA. Almost all of the examined Cxs were significantly decreased in the cochlear and semicircular ducts of yotari compared to wt and humans, except for Cx32, which was significantly higher in yotari. Cx40 dominated in human inner-ear development, while yotari and wt had decreased expression. The Panx1 expression in yotari was significantly lower than that in the wt and human inner ear, except at E13.5 in the mesenchyme of the wt and epithelium and mesenchyme of humans. Our results emphasize the relevance of GJIC during the development of vestibular and cochlear functions, where they can serve as potential therapeutic targets in inner-ear impairments.
Highlights
The inner ear is made up of the vestibular and cochlear segments, which develop from the otic vesicle, a specialized epithelial invagination of ectodermal origin that gives rise to specific sensory structures: the macula sacculi, macula utriculi, cristae ampullares, and cochlear duct [1]
In the sixth week of development, semicircular canals and the utricle had already developed from the vestibular portion, whereas the cochlear duct and the saccule had already developed from the cochlear region (Figure 1a)
Our data could provide important information for better understanding disorders that can arise during inner-ear development, since Cxs and Pannexin 1 (Panx1) seem to be key players in the maintenance of inner-ear homeostasis
Summary
The inner ear is made up of the vestibular and cochlear segments, which develop from the otic vesicle, a specialized epithelial invagination of ectodermal origin that gives rise to specific sensory structures: the macula sacculi, macula utriculi, cristae ampullares, and cochlear duct [1]. The progressive development of the human inner ear begins around the fourth week of gestation from the otic placodes towards the otic vesicle. The otic vesicle is divided into the ventral and dorsal components, from which the vestibular (semicircular canals and associated cristae, saccule, and utricle) and cochlear segments (cochlea) emerge. These segments provide balance and spatial orientation through the vestibular organ and hearing perception through the cochlea [2,3].
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