Connexin-Mediated Signaling in Nonsensory Cells Is Crucial for the Development of Sensory Inner Hair Cells in the Mouse Cochlea

• DOI: 10.1523/jneurosci.2251-16.2016
• Publication Date: 2016-11-19T03:50:22Z
• Authors: Stuart L. Johnson; Federico Ceriani; Oliver Houston; Roman Polishchuk; Elena Polishchuk; Giulia Crispino; Veronica Zorzi; Fabio Mammano; Walter Marcotti
• Keywords: Conditional gene knockout

Mutations in the genes encoding for gap junction proteins connexin 26 (Cx26) and 30 (Cx30) have been linked to syndromic nonsyndromic hearing loss mice humans. The release of ATP from hemichannels cochlear nonsensory cells has proposed be main trigger action potential activity immature sensory inner hair (IHCs), which is crucial refinement developing auditory circuitry. Using knock-out mice, we show that IHCs fire spontaneous potentials even absence ATP-dependent intercellular Ca 2+ signaling cells. However, this was able increase intrinsic IHC firing frequency. We also found expression key functional maturation. In Cx26 conditional ( Sox10-Cre ), maturation IHCs, normally occurs at approximately postnatal day 12, partially prevented. Although Cx30 shown not required young adult exhibited a comprehensive brake their development, such basolateral membrane currents synaptic machinery retain prehearing phenotype. propose differentiation into mature receptors initiated cochlea provided either reaches threshold level. As such, connexins regulate one most refinements mammalian cochlea, disruption contributes deafness phenotype observed DFNB1 patients. SIGNIFICANCE STATEMENT correct development function relies only on cells, but surrounding largely implicated general homeostasis involvement initial less clear. mutant mouse models common form congenital humans, are knock-outs gap-junction channels genes, defects prevented knock-outs, remained stuck stage and, as unable process sound information.