Axodendritic versus axosomatic cochlear efferent termination is determined by afferent type in a hierarchical logic of circuit formation

Webber, Jemma L.; Clancy, John; Zhou, Yingjie; Yraola, Natalia; Homma, Kazuaki; Garcı́a-Añoveros, Jaime

doi:10.1126/sciadv.abd8637

Cited by 8 publications

(5 citation statements)

References 73 publications

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“…7c ). This indicates that the proper formation of the tunnel of Corti is susceptible to the locally restricted loss of IHCs but that conversion of hair cells is not sufficient to induce the conversion of the underlying supporting cells as previously reported 42 .…”

Section: Resultssupporting

confidence: 58%

TBX2 specifies and maintains inner hair and supporting cell fate in the Organ of Corti

et al. 2022

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The auditory function of the mammalian cochlea relies on two types of mechanosensory hair cells and various non-sensory supporting cells. Recent studies identified the transcription factors INSM1 and IKZF2 as regulators of outer hair cell (OHC) fate. However, the transcriptional regulation of the differentiation of inner hair cells (IHCs) and their associated inner supporting cells (ISCs) has remained enigmatic. Here, we show that the expression of the transcription factor TBX2 is restricted to IHCs and ISCs from the onset of differentiation until adulthood and examine its function using conditional deletion and misexpression approaches in the mouse. We demonstrate that TBX2 acts in prosensory progenitors as a patterning factor by specifying the inner compartment of the sensory epithelium that subsequently gives rise to IHCs and ISCs. Hair cell-specific inactivation or misexpression causes transdifferentiation of hair cells indicating a cell-autonomous function of TBX2 in inducing and maintaining IHC fate.

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Section: Resultssupporting

confidence: 58%

TBX2 specifies and maintains inner hair and supporting cell fate in the Organ of Corti

et al. 2022

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“…However, although in other systems instructive signalling from neurons to their peripheral target cells are known to be crucial for the development of the targeted cells 57 , both IHC and OHC have been shown to develop in the absence of innervation 58 , 59 , we therefore here only focused on the outgoing HC to SGN signalling as it is more likely to represent an actual signalling network. Moreover, while OHCs are known to interact with I-SGNs, mostly through repulsive signals 26 , 60 , 61 , IHC to II-SGN negative interactions are more unlikely to occur at E18.5 60 and were then discarded from the analysis. Also, we filtered ligand-receptor modules based on their expression level and on the number of cells expressing the specific interactors as to provide higher confidence of their biological relevance.…”

Section: Resultsmentioning

confidence: 99%

Single-cell RNA-sequencing analysis of the developing mouse inner ear identifies molecular logic of auditory neuron diversification

et al. 2022

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Different types of spiral ganglion neurons (SGNs) are essential for auditory perception by transmitting complex auditory information from hair cells (HCs) to the brain. Here, we use deep, single cell transcriptomics to study the molecular mechanisms that govern their identity and organization in mice. We identify a core set of temporally patterned genes and gene regulatory networks that may contribute to the diversification of SGNs through sequential binary decisions and demonstrate a role for NEUROD1 in driving specification of a Ic-SGN phenotype. We also find that each trajectory of the decision tree is defined by initial co-expression of alternative subtype molecular controls followed by gradual shifts toward cell fate resolution. Finally, analysis of both developing SGN and HC types reveals cell-cell signaling potentially playing a role in the differentiation of SGNs. Our results indicate that SGN identities are drafted prior to birth and reveal molecular principles that shape their differentiation and will facilitate studies of their development, physiology, and dysfunction.

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“…It is not clear if the reduction was only limited to type II fibers or if type II and efferent fibers to OHCs were both affected. Most nerve fibers crossing the tunnel are efferent fibers from MOC ( Maison et al, 2016 ; Webber et al, 2021 ). We did not label these fibers using specific markers.…”

Section: Discussionmentioning

confidence: 99%

Deletion of C1ql1 Causes Hearing Loss and Abnormal Auditory Nerve Fibers in the Mouse Cochlea

Xiong

et al. 2021

Front. Cell. Neurosci.

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Complement C1q Like 1 (C1QL1), a secreted component of C1Q-related protein, is known to play an important role in synaptic maturation, regulation, and maintenance in the central nervous system. C1ql1 is expressed in adult cochlear inner and outer hair cells (IHCs and OHCs) with preferential expression in OHCs. We generated C1ql1 null mice to examine the role of C1QL1 in the auditory periphery. C1ql1-null mice exhibited progressive hearing loss with elevated thresholds of auditory brainstem response and distortion product otoacoustic emission. Confocal microscopy showed that the number of nerve fibers innervating both IHCs and OHCs was significantly reduced. However, spiral ganglion neurons appeared to be normal under electron microscopy. IHC development and survival were not affected by deletion of C1ql1. Voltage-clamp recording and immunocytochmistry combined with confocal microscopy showed C1ql1-null IHCs showed no significant reduction of pre-synaptic proteins and synaptic vesicle release. This is in contrast to significant OHC loss in the KO mice. Our study suggests that C1ql1 is essential for development of hair cell innervation and OHC survival. But maturation of presynaptic machinery in IHCs does not depend on C1QL1.

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Axodendritic versus axosomatic cochlear efferent termination is determined by afferent type in a hierarchical logic of circuit formation

Cited by 8 publications

References 73 publications

TBX2 specifies and maintains inner hair and supporting cell fate in the Organ of Corti

TBX2 specifies and maintains inner hair and supporting cell fate in the Organ of Corti

Single-cell RNA-sequencing analysis of the developing mouse inner ear identifies molecular logic of auditory neuron diversification

Deletion of C1ql1 Causes Hearing Loss and Abnormal Auditory Nerve Fibers in the Mouse Cochlea

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