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Irx3/5 Null Deletion in Mice Blocks Cochlea-Saccule Segregation and Disrupts the Auditory Tonotopic Map

B. Fritzsch, X. Weng, EN. Yamoah, T. Qin, CC. Hui, L. Lebrón-Mora, G. Pavlinkova, MH. Sham

. 2024 ; 532 (12) : e70008. [pub] -

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc25003135

Grantová podpora
R01 AG060504 NIA NIH HHS - United States
AG060504 NIH HHS - United States
AG051443 NIH HHS - United States

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.

Citace poskytuje Crossref.org

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