Document Type

Article

Publication Date

5-17-2021

Publication Title

Nat Commun

Keywords

JMG

JAX Source

Nat Commun 2021 May 17; 12(1):2861

Volume

12

Issue

1

First Page

2861

Last Page

2861

ISSN

2041-1723

PMID

34001891

DOI

https://doi.org/10.1038/s41467-021-22997-1

Grant

DC015242, DC018304

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.

Comments

We gratefully acknowledge the contribution of Rick Maser and the Genome Engineering Technology service at The Jackson Laboratory for assistance with creating the Emx2 mouse model. The Gpr156 mouse model was produced by the KOMP program led by Steve Murray at The Jackson Laboratory.

This article is licensed under a Creative Commons Attribution 4.0 International License.

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