Combined Atoh1 and Neurod1 Deletion Reveals Autonomous Growth of Auditory Nerve Fibers

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F20%3A00541345" target="_blank" >RIV/86652036:_____/20:00541345 - isvavai.cz</a>

Výsledek na webu

<a href="https://link.springer.com/article/10.1007%2Fs12035-020-02092-0" target="_blank" >https://link.springer.com/article/10.1007%2Fs12035-020-02092-0</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s12035-020-02092-0" target="_blank" >10.1007/s12035-020-02092-0</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Combined Atoh1 and Neurod1 Deletion Reveals Autonomous Growth of Auditory Nerve Fibers

Popis výsledku v původním jazyce

Ear development requires the transcription factors ATOH1 for hair cell differentiation and NEUROD1 for sensory neuron development. In addition, NEUROD1 negatively regulatesAtoh1gene expression. As we previously showed that deletion of theNeurod1gene in the cochlea results in axon guidance defects and excessive peripheral innervation of the sensory epithelium, we hypothesized that some of the innervation defects may be a result of abnormalities in NEUROD1 and ATOH1 interactions. To characterize the interdependency of ATOH1 and NEUROD1 in inner ear development, we generated a newAtoh1/Neurod1double null conditional deletion mutant. Through careful comparison of the effects of singleAtoh1orNeurod1gene deletion with combined doubleAtoh1andNeurod1deletion, we demonstrate that NEUROD1-ATOH1 interactions are not important for theNeurod1null innervation phenotype. We report that neurons lackingNeurod1can innervate the flat epithelium without any sensory hair cells or supporting cells left afterAtoh1deletion, indicating that neurons withNeurod1deletion do not require the presence of hair cells for axon growth. Moreover, transcriptome analysis identified genes encoding axon guidance and neurite growth molecules that are dysregulated in theNeurod1deletion mutant. Taken together, we demonstrate that much of the projections of NEUROD1-deprived inner ear sensory neurons are regulated cell-autonomously.

Název v anglickém jazyce

Combined Atoh1 and Neurod1 Deletion Reveals Autonomous Growth of Auditory Nerve Fibers

Popis výsledku anglicky

Ear development requires the transcription factors ATOH1 for hair cell differentiation and NEUROD1 for sensory neuron development. In addition, NEUROD1 negatively regulatesAtoh1gene expression. As we previously showed that deletion of theNeurod1gene in the cochlea results in axon guidance defects and excessive peripheral innervation of the sensory epithelium, we hypothesized that some of the innervation defects may be a result of abnormalities in NEUROD1 and ATOH1 interactions. To characterize the interdependency of ATOH1 and NEUROD1 in inner ear development, we generated a newAtoh1/Neurod1double null conditional deletion mutant. Through careful comparison of the effects of singleAtoh1orNeurod1gene deletion with combined doubleAtoh1andNeurod1deletion, we demonstrate that NEUROD1-ATOH1 interactions are not important for theNeurod1null innervation phenotype. We report that neurons lackingNeurod1can innervate the flat epithelium without any sensory hair cells or supporting cells left afterAtoh1deletion, indicating that neurons withNeurod1deletion do not require the presence of hair cells for axon growth. Moreover, transcriptome analysis identified genes encoding axon guidance and neurite growth molecules that are dysregulated in theNeurod1deletion mutant. Taken together, we demonstrate that much of the projections of NEUROD1-deprived inner ear sensory neurons are regulated cell-autonomously.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

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

Název periodika

Molecular Neurobiology

ISSN

0893-7648

e-ISSN

—

Svazek periodika

57

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

16

Strana od-do

5307-5323

Kód UT WoS článku

000565831800001

EID výsledku v databázi Scopus

2-s2.0-85090165942