Journal article
ISL1 is necessary for auditory neuron development and contributes toward tonotopic organization
Proceedings of the National Academy of Sciences - PNAS, Vol.119(37), pp.e2207433119-e2207433119
09/13/2022
DOI: 10.1073/pnas.2207433119
PMCID: PMC9478650
PMID: 36074819
Abstract
A cardinal feature of the auditory pathway is frequency selectivity, represented in a tonotopic 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 regulates the molecular and cellular features of auditory neurons, including the formation of the spiral ganglion and peripheral and central processes that shape the tonotopic representation 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 disrupted. The central axons of Isl1 mutants lose their topographic projections and segregation 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 disorganization 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 plasticity 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 structural and functional tonotopic maps. Still, upon Isl1 deletion, the ensuing central plasticity of the auditory pathway does not suffice to overcome developmentally induced peripheral dysfunction of the cochlea.
Details
- Title: Subtitle
- ISL1 is necessary for auditory neuron development and contributes toward tonotopic organization
- Creators
- Iva Filova - Czech Academy of SciencesKateryna Pysanenko - Czech Academy of SciencesMitra Tavakoli - Czech Academy of SciencesSimona Vochyanova - Czech Academy of SciencesMartina Dvorakova - Czech Academy of SciencesRomana Bohuslavova - Czech Academy of SciencesOndrej Smolik - Czech Academy of SciencesValeria Fabriciova - Czech Academy of SciencesPetra Hrabalova - Czech Academy of SciencesSarka Benesova - Czech Academy of Sciences, Institute of BiotechnologyLukas Valihrach - Czech Academy of Sciences, Institute of BiotechnologyJiri Cerny - Czech Academy of SciencesEbenezer N Yamoah - University of Nevada, Reno School of MedicineJosef Syka - Czech Academy of SciencesBernd Fritzsch - University of IowaGabriela Pavlinkova - Czech Academy of Sciences
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.119(37), pp.e2207433119-e2207433119
- DOI
- 10.1073/pnas.2207433119
- PMID
- 36074819
- PMCID
- PMC9478650
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- National Academy of Sciences
- Grant note
- DOI: 10.13039/501100001824, name: Czech Science Foundation, award: 20-06927S; DOI: 10.13039/501100004240, name: Akademie Věd České Republiky, award: 86652036; DOI: 10.13039/100000049, name: HHS | NIH | National Institute on Aging, award: AG060504; DOI: 10.13039/100000049, name: HHS | NIH | National Institute on Aging, award: AG051443; DOI: 10.13039/100000049, name: HHS | NIH | National Institute on Aging, award: DC016099
- Language
- English
- Date published
- 09/13/2022
- Academic Unit
- Iowa Neuroscience Institute; Biology; Craniofacial Anomalies Research Center
- Record Identifier
- 9984297352202771
Metrics
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