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

Kód výsledku v 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>

Nalezeny alternativní kódy

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

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10605 - Developmental biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

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

Název periodika

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

ISSN

0027-8424

e-ISSN

—

Svazek periodika

119

Číslo periodika v rámci svazku

37

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

e2207433119

Kód UT WoS článku

000895561900005

EID výsledku v databázi Scopus

2-s2.0-85139290572