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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F22%3A00568863" target="_blank" >RIV/68378041:_____/22:00568863 - isvavai.cz</a>

Alternative codes found

RIV/86652036:_____/22:00568863 RIV/68378050:_____/22:00568863

Result on the web

<a href="https://www.pnas.org/doi/full/10.1073/pnas.2207433119" target="_blank" >https://www.pnas.org/doi/full/10.1073/pnas.2207433119</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1073/pnas.2207433119" target="_blank" >10.1073/pnas.2207433119</a>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10605 - Developmental biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2022

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Proceedings of the National Academy of Sciences of the United States of America

ISSN

0027-8424

e-ISSN

—

Volume of the periodical

119

Issue of the periodical within the volume

37

Country of publishing house

US - UNITED STATES

Number of pages

12

Pages from-to

e2207433119

UT code for WoS article

000895561900005

EID of the result in the Scopus database

2-s2.0-85139290572