Bone morphogenetic protein 4 antagonizes hair cell regeneration in the avian auditory epithelium.

Bone morphogenetic protein 4 antagonizes hair cell regeneration in the avian auditory epithelium.
Hear Res. 2018 May 02;:
Authors: Lewis RM, Keller JJ, Wan L, Stone JS
Abstract
Permanent hearing loss is often a result of damage to cochlear hair cells, which mammals are unable to regenerate. Non-mammalian vertebrates such as birds replace damaged hair cells and restore hearing function, but mechanisms controlling regeneration are not understood. The secreted protein bone morphogenetic protein 4 (BMP4) regulates inner ear morphogenesis and hair cell development. To investigate mechanisms controlling hair cell regeneration in birds, we examined expression and function of BMP4 in the auditory epithelia (basilar papillae) of chickens of either sex after hair cell destruction by ototoxic antibiotics. In mature basilar papillae, BMP4 mRNA is highly expressed in hair cells, but not in hair cell progenitors (supporting cells). Supporting cells transcribe genes encoding receptors for BMP4 (BMPR1A, BMPR1B, and BMPR2) and effectors of BMP4 signaling (ID transcription factors). Following hair cell destruction, BMP4 transcripts are lost from the sensory epithelium. Using organotypic cultures, we demonstrate that treatments with BMP4 during hair cell destruction prevent supporting cells from upregulating expression of the pro-hair cell transcription factor ATOH1, entering the cell cycle, and fully transdifferentiating into hair cells, but they do n...

Source: Hearing Research - May 2, 2018 Category: Audiology Authors: Lewis RM, Keller JJ, Wan L, Stone JS Tags: Hear Res Source Type: research