Runx1 Controls Auditory Sensory Neuron Diversity in Mice

Overview

Journal Dev Cell

Publisher Cell Press

Specialties Cell Biology
Reproductive Medicine

Date 2023 Feb 21

PMID 36800995

Authors

Brikha R Shrestha

Lorna Wu

Lisa V Goodrich

Affiliations

Soon will be listed here.

Abstract

Sound stimulus is encoded in mice by three molecularly and physiologically diverse subtypes of sensory neurons, called Ia, Ib, and Ic spiral ganglion neurons (SGNs). Here, we show that the transcription factor Runx1 controls SGN subtype composition in the murine cochlea. Runx1 is enriched in Ib/Ic precursors by late embryogenesis. Upon the loss of Runx1 from embryonic SGNs, more SGNs take on Ia rather than Ib or Ic identities. This conversion was more complete for genes linked to neuronal function than to connectivity. Accordingly, synapses in the Ib/Ic location acquired Ia properties. Suprathreshold SGN responses to sound were enhanced in Runx1 mice, confirming the expansion of neurons with Ia-like functional properties. Runx1 deletion after birth also redirected Ib/Ic SGNs toward Ia identity, indicating that SGN identities are plastic postnatally. Altogether, these findings show that diverse neuronal identities essential for normal auditory stimulus coding arise hierarchically and remain malleable during postnatal development.

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References

Foldy C, Darmanis S, Aoto J, Malenka R, Quake S, Sudhof T . Single-cell RNAseq reveals cell adhesion molecule profiles in electrophysiologically defined neurons. Proc Natl Acad Sci U S A. 2016; 113(35):E5222-31. PMC: 5024636. DOI: 10.1073/pnas.1610155113. View

Chen C, Broom D, Liu Y, de Nooij J, Li Z, Cen C . Runx1 determines nociceptive sensory neuron phenotype and is required for thermal and neuropathic pain. Neuron. 2006; 49(3):365-77. DOI: 10.1016/j.neuron.2005.10.036. View

Meng X, Murali S, Cheng Y, Lu J, Hight A, Kanumuri V . Increasing the expression level of ChR2 enhances the optogenetic excitability of cochlear neurons. J Neurophysiol. 2019; 122(5):1962-1974. PMC: 6879948. DOI: 10.1152/jn.00828.2018. View

Allan D, Thor S . Transcriptional selectors, masters, and combinatorial codes: regulatory principles of neural subtype specification. Wiley Interdiscip Rev Dev Biol. 2015; 4(5):505-28. PMC: 4672696. DOI: 10.1002/wdev.191. View

Tan Y, Cahan P . SingleCellNet: A Computational Tool to Classify Single Cell RNA-Seq Data Across Platforms and Across Species. Cell Syst. 2019; 9(2):207-213.e2. PMC: 6715530. DOI: 10.1016/j.cels.2019.06.004. View

Hobert O . Regulation of terminal differentiation programs in the nervous system. Annu Rev Cell Dev Biol. 2011; 27:681-96. DOI: 10.1146/annurev-cellbio-092910-154226. View

Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T . Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012; 9(7):676-82. PMC: 3855844. DOI: 10.1038/nmeth.2019. View

Liberman L, Wang H, Liberman M . Opposing gradients of ribbon size and AMPA receptor expression underlie sensitivity differences among cochlear-nerve/hair-cell synapses. J Neurosci. 2011; 31(3):801-8. PMC: 3290333. DOI: 10.1523/JNEUROSCI.3389-10.2011. View

Sherrill H, Jean P, Driver E, Sanders T, Fitzgerald T, Moser T . Pou4f1 Defines a Subgroup of Type I Spiral Ganglion Neurons and Is Necessary for Normal Inner Hair Cell Presynaptic Ca Signaling. J Neurosci. 2019; 39(27):5284-5298. PMC: 6607758. DOI: 10.1523/JNEUROSCI.2728-18.2019. View

10.

Katz L, Shatz C . Synaptic activity and the construction of cortical circuits. Science. 1996; 274(5290):1133-8. DOI: 10.1126/science.274.5290.1133. View

11.

Growney J, Shigematsu H, Li Z, Lee B, Adelsperger J, Rowan R . Loss of Runx1 perturbs adult hematopoiesis and is associated with a myeloproliferative phenotype. Blood. 2005; 106(2):494-504. PMC: 1895175. DOI: 10.1182/blood-2004-08-3280. View

12.

Filova I, Pysanenko K, Tavakoli M, Vochyanova S, Dvorakova M, Bohuslavova R . ISL1 is necessary for auditory neuron development and contributes toward tonotopic organization. Proc Natl Acad Sci U S A. 2022; 119(37):e2207433119. PMC: 9478650. DOI: 10.1073/pnas.2207433119. View

13.

Yu W, Appler J, Kim Y, Nishitani A, Holt J, Goodrich L . A Gata3-Mafb transcriptional network directs post-synaptic differentiation in synapses specialized for hearing. Elife. 2013; 2:e01341. PMC: 3851837. DOI: 10.7554/eLife.01341. View

14.

Kujawa S, Liberman M . Synaptopathy in the noise-exposed and aging cochlea: Primary neural degeneration in acquired sensorineural hearing loss. Hear Res. 2015; 330(Pt B):191-9. PMC: 4567542. DOI: 10.1016/j.heares.2015.02.009. View

15.

Furman A, Kujawa S, Liberman M . Noise-induced cochlear neuropathy is selective for fibers with low spontaneous rates. J Neurophysiol. 2013; 110(3):577-86. PMC: 3742994. DOI: 10.1152/jn.00164.2013. View

16.

Petitpre C, Faure L, Uhl P, Fontanet P, Filova I, Pavlinkova G . Single-cell RNA-sequencing analysis of the developing mouse inner ear identifies molecular logic of auditory neuron diversification. Nat Commun. 2022; 13(1):3878. PMC: 9256748. DOI: 10.1038/s41467-022-31580-1. View

17.

Schmiedt R, Mills J, Boettcher F . Age-related loss of activity of auditory-nerve fibers. J Neurophysiol. 1996; 76(4):2799-803. DOI: 10.1152/jn.1996.76.4.2799. View

18.

Mevel R, Draper J, Lie-A-Ling M, Kouskoff V, Lacaud G . RUNX transcription factors: orchestrators of development. Development. 2019; 146(17). DOI: 10.1242/dev.148296. View

19.

Bharadwaj H, Verhulst S, Shaheen L, Liberman M, Shinn-Cunningham B . Cochlear neuropathy and the coding of supra-threshold sound. Front Syst Neurosci. 2014; 8:26. PMC: 3930880. DOI: 10.3389/fnsys.2014.00026. View

20.

Kolla L, Kelly M, Mann Z, Anaya-Rocha A, Ellis K, Lemons A . Characterization of the development of the mouse cochlear epithelium at the single cell level. Nat Commun. 2020; 11(1):2389. PMC: 7221106. DOI: 10.1038/s41467-020-16113-y. View