EBF1 Limits the Numbers of Cochlear Hair and Supporting Cells and Forms the Scala Tympani and Spiral Limbus during Inner Ear Development.

Early B-cell factor 1 (EBF1) is a basic helix-loop-helix transcription factor essential for the differentiation of various tissues. Our single-cell RNA sequencing data suggest that Ebf1 is expressed in the sensory epithelium of the mouse inner ear. Here, we found that the murine Ebf1 gene and its protein are expressed in the prosensory domain of the inner ear, medial region of the cochlear duct floor, otic mesenchyme, and cochleovestibular ganglion. Ebf1 deletion in mice results in incomplete formation of the spiral limbus and scala tympani, increased number of cells in the organ of Corti and Kölliker's organ, and aberrant course of the spiral ganglion axons. Ebf1 deletion in the mouse cochlear epithelia caused the proliferation of SOX2-positive cochlear cells at E13.5, indicating that EBF1 suppresses the proliferation of the prosensory domain and cells of Kölliker's organ to facilitate the development of appropriate numbers of hair and supporting cells. Furthermore, mice with deletion of cochlear epithelium-specific Ebf1 showed poor postnatal hearing function. Our results suggest that Ebf1 is essential for normal auditory function in mammals.

Outcome of regenerative therapy for age-related vocal fold atrophy with basic fibroblast growth factor.

OBJECTIVES/HYPOTHESIS: Age-related vocal fold atrophy has become a significant voice disorder as the elderly population grows. However, several therapeutic challenges have limited attempts to improve voice quality. We reported that basic fibroblast growth factor (bFGF) stimulates fibroblasts to produce extracellular matrices such as hyaluronic acid in the lamina propria, leading to a regeneration of pliable vocal folds in animal models. The aim of this study was to determine the efficacy of bFGF for the treatment of age-related vocal fold atrophy. STUDY DESIGN: Prospective study. METHODS: Six patients with age-related vocal fold atrophy underwent injection of bFGF in their vocal folds. Vocal outcomes and stroboscopic examinations were evaluated 1, 3, and 6 months after the injection. The outcome measures included the Voice Handicap Index-10 (VHI-10), GRBAS (grade, roughness, breathiness, asthenia, strain) scale, maximum phonation time (MPT), the amplitude perturbation quotient (APQ), and the pitch perturbation quotient (PPQ). RESULTS: The VHI-10 was significantly improved 6 months after bFGF injection. The GRBAS scale, MPT, APQ, and PPQ were also improved. Stroboscopic examinations showed significant improvement of glottic closure and better mucosal wave. CONCLUSIONS: This is the first study to evaluate the regenerative effects of bFGF injection for the treatment of age-related vocal fold atrophy using the VHI-10. Injection of bFGF significantly improved VHI-10 scores and glottal insufficiency for at least 6 months. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:1844-1848, 2016.