ArticleDevelopment (Cambridge, England)2024
Jag1 represses Notch activation in lateral supporting cells and inhibits an outer hair cell fate in the medial cochlea.
Article in Development (Cambridge, England), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Bilateral acute mastoiditis during Epstein-Barr virus infection in a child with alagille syndrome: a case report and scoping review.Italian journal of pediatrics · 2026Article
- Reproductive-state dependent changes in inner ear gene expression in female plainfin midshipman fish.PloS one · 2026Article
- Wnt/PKC Signaling Inhibits Sensory Hair Cell Formation in the Developing Mammalian Cochlea.Cells · 2025Article
- Applying the algorithm for Proven and young in GWAS Reveals high polygenicity for key traits in Nellore cattle.Frontiers in genetics · 2025Article
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9 authors.
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Abstract
Notch signaling patterns the cochlear organ of Corti, and individuals with the JAG1/NOTCH2-related genetic disorder Alagille syndrome can thus experience hearing loss. We investigated the function of Jag1 in cochlear patterning and signaling using Jag1Ndr/Ndr mice, which are a model of Alagille syndrome. Jag1Ndr/Ndr mice exhibited expected vestibular and auditory deficits, a dose-dependent increase in ectopic inner hair cells, and a reduction in outer hair cells. Single cell RNA sequencing of the organ of Corti demonstrated a global dysregulation of genes associated with inner ear development and deafness. Analysis of individual cell types further revealed that Jag1 represses Notch activation in lateral supporting cells and demonstrated a function for Jag1 in gene regulation and development of outer hair cells. Surprisingly, ectopic 'outer hair cell-like' cells were present in the medial compartment and pillar cell region of Jag1Ndr/Ndr cochleae, yet they exhibited location-dependent expression of the inner hair cell fate-determinant Tbx2, suggesting Jag1 is required for Tbx2 to drive inner hair cell commitment. This study thus identifies new roles for Jag1 in supporting cells, and in outer hair cell specification and positioning.
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