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ISL1 is necessary for auditory neuron development and contributes toward tonotopic organization
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SYSNO ASEP 0568863 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title ISL1 is necessary for auditory neuron development and contributes toward tonotopic organization Author(s) Filova, Iva (BTO-N) ORCID
Pysaněnko, Kateryna (UEM-P) ORCID
Tavakoli, Mitra (BTO-N)
Vochyánová, Simona (BTO-N)
Dvořáková, Martina (BTO-N) ORCID
Bohuslavová, Romana (BTO-N) RID
Smolík, Ondřej (BTO-N)
Fabriciová, Valeria (BTO-N)
Hrabalová, Petra (BTO-N) RID
Benešová, Šárka (BTO-N)
Valihrach, Lukáš (BTO-N) RID, ORCID
Černý, Jiří (UMG-J)
Yamoah, E. N. (US)
Syka, Josef (UEM-P) RID
Fritzsch, B. (US)
Pavlínková, Gabriela (BTO-N) RID, ORCIDNumber of authors 16 Article number e2207433119 Source Title Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences - ISSN 0027-8424
Roč. 119, č. 37 (2022)Number of pages 12 s. Language eng - English Country US - United States Keywords spiral ganglion neurons ; auditory nuclei ; inferior colliculus ; auditory maps ; auditory behavior Subject RIV FH - Neurology OECD category Neurosciences (including psychophysiology R&D Projects GA20-06927S GA ČR - Czech Science Foundation (CSF) LM2018129 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) EF18_046/0016045 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) EF18_046/0015861 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LM2018126 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support BTO-N - RVO:86652036 ; UEM-P - RVO:68378041 ; UMG-J - RVO:68378050 UT WOS 000895561900005 EID SCOPUS 85139290572 DOI 10.1073/pnas.2207433119 Annotation A cardinal feature of the auditory pathway is frequency selectivity, represented in a tono-topic map from the cochlea to the cortex. The molecular determinants of the auditory frequency map are unknown. Here, we discovered that the transcription factor ISL1 reg-ulates the molecular and cellular features of auditory neurons, including the formation of the spiral ganglion and peripheral and central processes that shape the tonotopic rep-resentation of the auditory map. We selectively knocked out Isl1 in auditory neurons using Neurod1Cre strategies. In the absence of Isl1, spiral ganglion neurons migrate into the central cochlea and beyond, and the cochlear wiring is profoundly reduced and dis-rupted. The central axons of Isl1 mutants lose their topographic projections and segrega-tion at the cochlear nucleus. Transcriptome analysis of spiral ganglion neurons shows that Isl1 regulates neurogenesis, axonogenesis, migration, neurotransmission-related machinery, and synaptic communication patterns. We show that peripheral disorganiza-tion in the cochlea affects the physiological properties of hearing in the midbrain and auditory behavior. Surprisingly, auditory processing features are preserved despite the significant hearing impairment, revealing central auditory pathway resilience and plastic-ity in Isl1 mutant mice. Mutant mice have a reduced acoustic startle reflex, altered prepulse inhibition, and characteristics of compensatory neural hyperactivity centrally. Our findings show that ISL1 is one of the obligatory factors required to sculpt auditory struc-tural and functional tonotopic maps. Still, upon Isl1 deletion, the ensuing central plastic-ity of the auditory pathway does not suffice to overcome developmentally induced peripheral dysfunction of the cochlea. Workplace Institute of Biotechnology Contact Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700 Year of Publishing 2023 Electronic address https://www.pnas.org/doi/full/10.1073/pnas.2207433119
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