Live imaging of hair bundle polarity acquisition demonstrates a critical timeline for transcription factor Emx2

Tona, Yosuke; Wu, Doris K.

doi:10.7554/elife.59282

Cited by 12 publications

(15 citation statements)

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“…Recent work found that the transcription factor EMX2 breaks the uniform orientation defined by core PCP proteins in mouse maculae and zebrafish neuromasts [27][28][29][30][31] . Emx2 is regionally expressed in just one HC population (Fig.…”

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confidence: 99%

EMX2-GPR156-Gαi reverses hair cell orientation in mechanosensory epithelia

et al. 2021

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Hair cells detect sound, head position or water movements when their mechanosensory hair bundle is deflected. Each hair bundle has an asymmetric architecture that restricts stimulus detection to a single axis. Coordinated hair cell orientations within sensory epithelia further tune stimulus detection at the organ level. Here, we identify GPR156, an orphan GPCR of unknown function, as a critical regulator of hair cell orientation. We demonstrate that the transcription factor EMX2 polarizes GPR156 distribution, enabling it to signal through Gαi and trigger a 180° reversal in hair cell orientation. GPR156-Gαi mediated reversal is essential to establish hair cells with mirror-image orientations in mouse otolith organs in the vestibular system and in zebrafish lateral line. Remarkably, GPR156-Gαi also instructs hair cell reversal in the auditory epithelium, despite a lack of mirror-image organization. Overall, our work demonstrates that conserved GPR156-Gαi signaling is integral to the framework that builds directional responses into mechanosensory epithelia.

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confidence: 99%

EMX2-GPR156-Gαi reverses hair cell orientation in mechanosensory epithelia

et al. 2021

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“…At early stages, this could reverse the orientation of the basal body shift, which in turn would reverse the orientation of the whole asymmetrical HC cytoskeleton. Support for a reversed shift of the basal body across the LPR was indeed obtained using live-imaging of explanted utricles ( Tona and Wu, 2020 ). Of note, these studies collectively demonstrate that HC orientation is not only regulated by intercellular mechanisms acting at the tissue level (core PCP), but also by a mechanism acting at the single cell level (Emx2-triggered reversal).…”

Section: A Regional Reversal In Hair Cell Orientation Produces Mirror-image Anatomy In Macular and Neuromast Organsmentioning

confidence: 74%

A Reversal in Hair Cell Orientation Organizes Both the Auditory and Vestibular Organs

Tarchini

2021

Front. Neurosci.

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Sensory hair cells detect mechanical stimuli with their hair bundle, an asymmetrical brush of actin-based membrane protrusions, or stereocilia. At the single cell level, stereocilia are organized in rows of graded heights that confer the hair bundle with intrinsic directional sensitivity. At the organ level, each hair cell is precisely oriented so that its intrinsic directional sensitivity matches the direction of mechanical stimuli reaching the sensory epithelium. Coordinated orientation among neighboring hair cells usually ensures the delivery of a coherent local group response. Accordingly, hair cell orientation is locally uniform in the auditory and vestibular cristae epithelia in birds and mammals. However, an exception to this rule is found in the vestibular macular organs, and in fish lateral line neuromasts, where two hair cell populations show opposing orientations. This mirror-image hair cell organization confers bidirectional sensitivity at the organ level. Here I review our current understanding of the molecular machinery that produces mirror-image organization through a regional reversal of hair cell orientation. Interestingly, recent evidence suggests that auditory hair cells adopt their normal uniform orientation through a global reversal mechanism similar to the one at work regionally in macular and neuromast organs. Macular and auditory organs thus appear to be patterned more similarly than previously appreciated during inner ear development.

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“…5). Vestibular bers entering the maculae begin to be segregated at around E14.5 16 , at which time most HCs have not formed yet 27 but the regional expression of Emx2 in the sensory epithelium is already well-established 22 . Together, these results support the hypothesis that Emx2 within the sensory epithelium/supporting cells guides the initial spatial segregation of the two types of afferents, namely those that project to the cerebellum versus brainstem.…”

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confidence: 99%

“…Since Emx2 expression spans from luminal to basal side of the sensory epithelium 13,22 , we addressed whether Emx2 expression in HCs alone is required for both establishing hair bundle orientation and neuronal selectivity by using G 1 cre 20 , a HC-speci c cre strain and a oxed allele (F) of Emx2 (Fig. 3).…”

Section: Mild Disruption Of Neuronal Segregation Pattern In Emx2 Cko ...mentioning

confidence: 99%

Function of bidirectional sensitivity in the otolith organs established by transcription factor Emx2

Tona

Wafa

et al. 2022

Preprint

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A conserved line of polarity reversal (LPR) demarcates hair cells into two regions of opposite orientation in the otolith organs of the inner ear. The functional significance of this arrangement is not known. Using gene knockout and conditional knockouts (cKO) mice, we show that the Emx2 encoded transcription factor establishes the LPR and bidirectional sensitivity of the otolith organ by mediating hair bundle orientation in HCs and neuronal selectivity in HCs and supporting cells. In addition to Emx2 cKO, we generated another mouse strain without bidirectional sensitivity in otolith organs, Tmie cKO, in which HCs within the Emx2 expression domain lack mechanotransduction and thus are rendered non-functional. Behavioral analyses of both Emx2 cKO and Tmie cKO mice indicate that the LPR is specifically required for mice to swim comfortably and to traverse a balance beam efficiently, but LPR is not required for mice to stay on a rotating rod.

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Live imaging of hair bundle polarity acquisition demonstrates a critical timeline for transcription factor Emx2

Cited by 12 publications

References 56 publications

EMX2-GPR156-Gαi reverses hair cell orientation in mechanosensory epithelia

EMX2-GPR156-Gαi reverses hair cell orientation in mechanosensory epithelia

A Reversal in Hair Cell Orientation Organizes Both the Auditory and Vestibular Organs

Function of bidirectional sensitivity in the otolith organs established by transcription factor Emx2

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