The Interplay of Cx26, Cx32, Cx37, Cx40, Cx43, Cx45, and Panx1 in Inner-Ear Development of Yotari (dab1−/−) Mice and Humans

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.

The Expression of Connexin 37, 40, 43, 45 and Pannexin 1 in the Early Human Retina and Choroid Development and Tumorigenesis

“…However, we did not find any studies exploring Cx45 in the retinoblastoma and uveal melanoma. In our previous study, we also find Cx45 not to be relevant either in the yotari mice inner ear development (E13.5 and E15.5) or in the 8th week of developing human inner ear [ 12 ]. Our result might imply that Cx45 is not as relevant in the fetal and postnatal period as it is during early human eye development (8th and 10th developmental week) when normal patterning is ensured, especially in the retina.…”

“…Special proteins called connexins (Cxs) form hemichannels at the level of the cell membrane which connect intracellular and extracellular spaces, or form gap junctions between the neighboring cells [ 12 , 13 ]. As retinal and choroid cells are extensively coupled with gap junctional communications, this might be an important network that enables their metabolic homoeostasis [ 14 , 15 ].…”