Scientists have identified transcription factors key to the developing auditory hair cells in mice, increasing understanding of hair cell development, with potential for future applications in hearing loss.
Sensorineural hearing loss due to loss of auditory hair cells, the cells responsible for hearing, is irreversible. This is because the auditory hair cells are not capable of regenerating. A recent landmark study that has been published in the journal Nature Communications, has identified key transcription factors that play a central role in hair cell development.
A team led by researchers at the University of Maryland School of Medicine set out to define the molecular signaling pathways that result in differentiation of hair cells, a step that would be critical for restoration of hearing following loss of auditory hair cells. Following analysis of gene expression within these auditory hair cells, the team identified a group of transcription factors, Rfx 1,2,3,5 and 7. In subsequent experiments the team found these transcription factors were necessary for proper hearing function in mice. Experiments in mice that did not express these transcription factors demonstrated that while the hair cells appeared to develop normally, they did not survive, resulting in hearing loss that caused profound deafness in mice by the time they were 3 months old. These set of experiments demonstrated that not only were the transcription factors found to be essential differentiation of auditory hair cells, but also for the survival of these specialized cells.
The study sheds light on molecular signaling pathways that are essential in the development and survival of specialized auditory hair cells that are necessary for hearing. The team aims to conduct further research to determine whether manipulation of this signaling pathway is possible for potential application of regenerative treatments for hearing loss.
Ran Elkon, Beatrice Milon, Laura Morrison, Manan Shah, Sarath Vijayakumar, Manoj Racherla, Carmen C. Leitch, Lorna Silipino, Shadan Hadi, Michèle Weiss-Gayet, Emmanuèle Barras, Christoph D. Schmid, Aouatef Ait-Lounis, Ashley Barnes, Yang Song, David J. Eisenman, Efrat Eliyahu, Gregory I. Frolenkov, Scott E. Strome, Bénédicte Durand, Norann A. Zaghloul, Sherri M. Jones, Walter Reith, Ronna Hertzano. “RFX transcription factors are essential for hearing in mice.” Nature Communications, 2015; 6: 8549 DOI: 10.1038/ncomms9549
Written by Deborah Tallarigo, PhD