{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Hayashi Y"],"funding":["HHS | NIH | National Institute on Deafness and Other Communication Disorders"],"pagination":["e2106369118"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8488680"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["118(39)"],"pubmed_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."],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["Norrie disease protein is essential for cochlear hair cell maturation."],"pmcid":["PMC8488680"],"funding_grant_id":["DC014089","DC017166"],"pubmed_authors":["Chiang H","Hayashi Y","Tian C","Indzhykulian AA","Edge ASB"],"additional_accession":[]},"is_claimable":false,"name":"Norrie disease protein is essential for cochlear hair cell maturation.","description":"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.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Sep","modification":"2025-04-04T19:58:06.367Z","creation":"2025-04-04T19:58:06.367Z"},"accession":"S-EPMC8488680","cross_references":{"pubmed":["34544869"],"doi":["10.1073/pnas.2106369118"]}}