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Publication : Ephrin-A3 is required for tonotopic map precision and auditory functions in the mouse auditory brainstem.

First Author  Hoshino N Year  2021
Journal  J Comp Neurol Volume  529
Issue  16 Pages  3633-3654
PubMed ID  34235739 Mgi Jnum  J:314922
Mgi Id  MGI:6828668 Doi  10.1002/cne.25213
Citation  Hoshino N, et al. (2021) Ephrin-A3 is required for tonotopic map precision and auditory functions in the mouse auditory brainstem. J Comp Neurol 529(16):3633-3654
abstractText  Tonotopy is a prominent feature of the vertebrate auditory system and forms the basis for sound discrimination, but the molecular mechanism that underlies its formation remains largely elusive. Ephrin/Eph signaling is known to play important roles in axon guidance during topographic mapping in other sensory systems, so we investigated its possible role in the establishment of tonotopy in the mouse cochlear nucleus. We found that ephrin-A3 molecules are differentially expressed along the tonotopic axis in the cochlear nucleus during innervation. Ephrin-A3 forward signaling is sufficient to repel auditory nerve fibers in a developmental stage-dependent manner. In mice lacking ephrin-A3, the tonotopic map is degraded and isofrequency bands of neuronal activation upon pure tone exposure become imprecise in the anteroventral cochlear nucleus. Ephrin-A3 mutant mice also exhibit a delayed second wave in auditory brainstem responses upon sound stimuli and impaired detection of sound frequency changes. Our findings establish an essential role for ephrin-A3 in forming precise tonotopy in the auditory brainstem to ensure accurate sound discrimination.
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