{Reference Type}: Journal Article
{Title}: Norrie disease protein is essential for cochlear hair cell maturation.
{Author}: Hayashi Y;Chiang H;Tian C;Indzhykulian AA;Edge ASB;
{Journal}: Proc Natl Acad Sci U S A
{Volume}: 118
{Issue}: 39
{Year}: 09 2021 28
{Factor}: 12.779
{DOI}: 10.1073/pnas.2106369118
{Abstract}: Mutations in the gene for Norrie disease protein (Ndp) cause syndromic deafness and blindness. We show here that cochlear function in an Ndp knockout mouse deteriorated with age: At P3-P4, hair cells (HCs) showed progressive loss of Pou4f3 and Gfi1, key transcription factors for HC maturation, and Myo7a, a specialized myosin required for normal function of HC stereocilia. Loss of expression of these genes correlated to increasing HC loss and profound hearing loss by 2 mo. We show that overexpression of the Ndp gene in neonatal supporting cells or, remarkably, up-regulation of canonical Wnt signaling in HCs rescued HCs and cochlear function. We conclude that Ndp secreted from supporting cells orchestrates a transcriptional network for the maintenance and survival of HCs and that increasing the level of β-catenin, the intracellular effector of Wnt signaling, is sufficient to replace the functional requirement for Ndp in the cochlea.