Norrie disease protein is essential for cochlear hair cell maturation.
Proc Natl Acad Sci U S A
; 118(39)2021 09 28.
Article
in En
| MEDLINE
| ID: mdl-34544869
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 ß-catenin, the intracellular effector of Wnt signaling, is sufficient to replace the functional requirement for Ndp in the cochlea.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transcription Factors
/
Homeodomain Proteins
/
DNA-Binding Proteins
/
Transcription Factor Brn-3C
/
Eye Proteins
/
Hair Cells, Auditory
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Hearing Loss
/
Nerve Tissue Proteins
Type of study:
Etiology_studies
Limits:
Animals
Language:
En
Journal:
Proc Natl Acad Sci U S A
Year:
2021
Document type:
Article