Journal article
Irx3/5 Null Deletion in Mice Blocks Cochlea‐Saccule Segregation and Disrupts the Auditory Tonotopic Map
Journal of comparative neurology (1911), Vol.532(12), e70008
12/01/2024
DOI: 10.1002/cne.70008
PMCID: PMC11629443
PMID: 39655644
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.
Deletion mutant of
Irx3
/
5
shows the cochlear base fused with the saccule, whereas in wild‐type mice, the saccule is separated from the base by the ductus reuniens.
Irx3
and
Irx5
are potential evolutionary branch‐point genes necessary for balance‐sound segregation.
Details
- Title: Subtitle
- Irx3/5 Null Deletion in Mice Blocks Cochlea‐Saccule Segregation and Disrupts the Auditory Tonotopic Map
- Creators
- Bernd Fritzsch - University of Nebraska Medical CenterXin Weng - Chinese University of Hong KongEbenezer N. Yamoah - University of ArizonaTianli Qin - Chinese University of Hong KongChi‐Chung Hui - Hospital for Sick ChildrenLaura Lebrón-Mora - Czech Academy of Sciences, Institute of BiotechnologyGabriela Pavlinkova - Czech Academy of Sciences, Institute of BiotechnologyMai Har Sham - Chinese University of Hong Kong
- Resource Type
- Journal article
- Publication Details
- Journal of comparative neurology (1911), Vol.532(12), e70008
- DOI
- 10.1002/cne.70008
- PMID
- 39655644
- PMCID
- PMC11629443
- NLM abbreviation
- J Comp Neurol
- ISSN
- 0021-9967
- eISSN
- 1096-9861
- Publisher
- John Wiley and Sons Inc
- Grant note
- National Institutes of Health
We thank members of our laboratories for their comments on this manuscript. We thank Jennifer Kersigo for helping with SEM. A special thanks to Robin M Taylor for helping with Figure 7.
- Language
- English
- Date published
- 12/01/2024
- Academic Unit
- Biology; Craniofacial Anomalies Research Center
- Record Identifier
- 9984756231002771
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