AUTHOR=Singh Jarnail , Randle Michelle R. , Walters Bradley J. , Cox Brandon C. 

TITLE=The transcription factor Pou4f3 is essential for the survival of postnatal and adult mouse cochlear hair cells and normal hearing

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=18

YEAR=2024

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2024.1369282

DOI=10.3389/fncel.2024.1369282

ISSN=1662-5102

ABSTRACT=<sec><title>Introduction</title><p>Hair cells (HCs) of the cochlea are responsible for sound transduction and hearing perception in mammals. Genetic mutations in the transcription factor <italic>Pou4f3</italic> cause non-syndromic autosomal dominant hearing loss in humans (DFNA15) which varies in the age of onset depending on the individual mutation. Mouse models with germline deletion or mutations in <italic>Pou4f3</italic> have previously demonstrated its critical role in the maturation and survival of cochlear HCs during embryonic development. However, the role of <italic>Pou4f3</italic> in auditory function and in the survival or maintenance of cochlear HCs after birth and during adulthood has not been studied.</p></sec><sec><title>Methods</title><p>Therefore, using the inducible CreER-loxP system, we deleted <italic>Pou4f3</italic> from mouse cochlear HCs at different postnatal ages, relevant to specific stages of HC maturation and hearing function.</p></sec><sec><title>Results and discussion</title><p>Elevated auditory brainstem response thresholds and significant HC loss were detected in mice with <italic>Pou4f3</italic> deletion compared to their control littermates, regardless of the age when <italic>Pou4f3</italic> was deleted. However, HC loss occurred more rapidly when <italic>Pou4f3</italic> was deleted from immature HCs. Additionally, HC loss caused by <italic>Pou4f3</italic> deletion did not affect the number of cochlear supporting cells, but caused a delayed loss of spiral ganglion neurons at 4 months after the deletion. In conclusion, <italic>Pou4f3</italic> is necessary for the survival of cochlear HCs and normal hearing at all postnatal ages regardless of their maturation state. Our data also suggest that <italic>Pou4f3</italic> indirectly regulates the survival of spiral ganglion neurons.</p></sec>