ArticleThe Journal of comparative neurology2024
Irx3/5 Null Deletion in Mice Blocks Cochlea-Saccule Segregation and Disrupts the Auditory Tonotopic Map.
Article in The Journal of comparative neurology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Regulatory Networks Driving the Specification, Differentiation, and Diversification of Neurons in the Mouse Inner Ear.Journal of the Association for Research in Otolaryngology : JARO · 2026Review
- Dicer Deletion in the Ear Can Cut Most Neurons and Their Innervation of Hair Cells to Project to the Ear and the Brainstem.International journal of molecular sciences · 2026Article
- Article
- Molecular Cascades That Build and Connect Auditory Neurons from Hair Cells to the Auditory Cortex.Journal of experimental neurology · 2025Article
- Article
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8 authors.
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Abstract
A gene cadre orchestrates the normal development of sensory and non-sensory cells in the inner ear, segregating the cochlea with a distinct tonotopic sound frequency map, similar brain projection, and five vestibular end-organs. However, the role of genes driving the ear development is largely unknown. Here, we show double deletion of the Iroquois homeobox 3 and 5 transcription factors (Irx3/5 DKO) leads to the fusion of the saccule and the cochlear base. The overlying otoconia and tectorial membranes are absent in the Irx3/5 DKO inner ear, and the primary auditory neurons project fibers to both the saccule and cochlear hair cells. The central neuronal projections from the cochlear apex-base contour are not fully segregated into a dorsal and ventral innervation in the Irx3/5 DKO cochlear nucleus, obliterating the characteristic tonotopic auditory map. Additionally, Irx3/5 deletion reveals a pronounced cochlear-apex-vestibular "vestibular-cochlear" nerve (VCN) bilateral connection that is less noticeable in wild-type control mice. Moreover, the incomplete segregation of apex and base projections that expands fibers to connect with vestibular nuclei. The results suggest the mammalian cochlear apex is a derived lagena reminiscent of sarcopterygians. Thus, Irx3 and 5 are potential evolutionary branch-point genes necessary for balance-sound segregation, which fused into a saccule-cochlea organization.
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