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

Katie S. Kindt, Anil Akturk, Amandine Jarysta, Matthew Day, Alisha Beirl, Michaela Flonard and Basile Tarchini ()
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Katie S. Kindt: Section on Sensory Cell Development and Function, National Institute on Deafness and Other Communication Disorders, National Institutes of Health
Anil Akturk: The Jackson Laboratory
Amandine Jarysta: The Jackson Laboratory
Matthew Day: The Jackson Laboratory
Alisha Beirl: Section on Sensory Cell Development and Function, National Institute on Deafness and Other Communication Disorders, National Institutes of Health
Michaela Flonard: The Jackson Laboratory
Basile Tarchini: The Jackson Laboratory

Nature Communications, 2021, vol. 12, issue 1, 1-19

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41467-021-22997-1

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