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| Status |
Public on Sep 01, 2022 |
| Title |
ISL1 is an essential determinant of structural and functional tonotopic representation of sound |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
A cardinal feature of the auditory pathway is frequency selectivity represented in the form of 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 features of auditory neurons, including the formation of the spiral ganglion neuron (SGN) 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, SGNs migrate into the central cochlea and beyond. 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 SGNs shows that Isl1 regulates neurogenesis, axonogenesis, migration, and the functional properties of neurons. Surprisingly, notable auditory processing features are preserved despite the significant hearing impairment, revealing central auditory pathway resilience and plasticity in mutant mice. Mutant mice demonstrate altered acoustic startle reflex, prepulse inhibition, characteristics of compensatory neural hyperactivity centrally. Our findings show that the Isl1 is one of the obligatory factors required to sculpt auditory structural and functional tonotopic maps. Still, upon Isl1 deletion, the ensuing compensatory plasticity of the auditory pathway does not suffice to overcome developmental changes at the peripheral sensory organ.
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| Overall design |
12 samples are analyzed (biological replicates of 6 control and 6 mutant samples) each containing 100 FACS-sorted tdTomato+ neurons.
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| Contributor(s) |
Filova I, Pysanenko K, Tavakoli M, Vochyanova S, Dvorakova M, Bohuslavova R, Smolik O, Benesova S, Valihrach L, Yamoah EN, Syka J, Fritzsch B, Pavlinkova G |
| Citation(s) |
36074819 |
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| Submission date |
Aug 23, 2021 |
| Last update date |
Dec 01, 2022 |
| Contact name |
Šárka Benešová |
| E-mail(s) |
sarka.benesova@ibt.cas.cz
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| Organization name |
Czech Academy of Science
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| Department |
Institute of Biotechnology
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| Lab |
Laboratory of Gene Expression
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| Street address |
Prumyslova 595
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| City |
Vestec |
| ZIP/Postal code |
25250 |
| Country |
Czech Republic |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA756951 |
| SRA |
SRP333689 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE182575_count_matrix.txt.gz |
489.7 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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