ISL1 is necessary for auditory neuron development and contributes toward tonotopic organization

0568863 - BTÚ 2023 RIV US eng J - Článek v odborném periodiku
Filova, Iva - Pysaněnko, Kateryna - Tavakoli, Mitra - Vochyánová, Simona - Dvořáková, Martina - Bohuslavová, Romana - Smolík, Ondřej - Fabriciová, Valeria - Hrabalová, Petra - Benešová, Šárka - Valihrach, Lukáš - Černý, Jiří - Yamoah, E. N. - Syka, Josef - Fritzsch, B. - Pavlínková, Gabriela
ISL1 is necessary for auditory neuron development and contributes toward tonotopic organization.
Proceedings of the National Academy of Sciences of the United States of America. Roč. 119, č. 37 (2022), č. článku e2207433119. ISSN 0027-8424. E-ISSN 1091-6490
Grant CEP: GA ČR(CZ) GA20-06927S; GA MŠMT(CZ) LM2018129; GA MŠMT(CZ) EF18_046/0016045; GA MŠMT EF18_046/0015861; GA MŠMT(CZ) LM2018126
Institucionální podpora: RVO:86652036 ; RVO:68378041 ; RVO:68378050
Klíčová slova: spiral ganglion neurons * auditory nuclei * inferior colliculus * auditory maps * auditory behavior
Obor OECD: Neurosciences (including psychophysiology; Developmental biology (UEM-P)
Impakt faktor: 11.1, rok: 2022
Způsob publikování: Open access
https://www.pnas.org/doi/full/10.1073/pnas.2207433119

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.
Trvalý link: https://hdl.handle.net/11104/0340313