Document Type
Article
Publication Date
11-12-2024
Original Citation
Ono K,
Jarysta A,
Hughes N,
Jukic A,
Chang H,
Deans M,
Eatock R,
Cullen K,
Kindt K,
Tarchini B.
Contributions of mirror-image hair cell orientation to mouse otolith organ and zebrafish neuromast function. Elife. 2024;13:RP97674.
Keywords
JMG, Animals, Zebrafish, Mice, Otolithic Membrane, Hair Cells, Auditory, Transcription Factors, Homeodomain Proteins, Mechanotransduction, Cellular, Lateral Line System, Zebrafish Proteins
JAX Source
Elife. 2024;13:RP97674.
ISSN
2050-084X
PMID
39531034
DOI
https://doi.org/10.7554/eLife.97674
Grant
This work was supported by the National Institute on Deafness and Other Communication Disorders (NIDCD) grant R01DC018304 (to RAE, KEC and BT), R01DC015242 (to BT) and NIDCD Intramural Research Program Grant 1ZIADC000085-01 (to KK)
Abstract
Otolith organs in the inner ear and neuromasts in the fish lateral-line harbor two popu- lations of hair cells oriented to detect stimuli in opposing directions. The underlying mechanism is highly conserved: the transcription factor EMX2 is regionally expressed in just one hair cell popu- lation and acts through the receptor GPR156 to reverse cell orientation relative to the other popu- lation. In mouse and zebrafish, loss of Emx2 results in sensory organs that harbor only one hair cell orientation and are not innervated properly. In zebrafish, Emx2 also confers hair cells with reduced mechanosensory properties. Here, we leverage mouse and zebrafish models lacking GPR156 to determine how detecting stimuli of opposing directions serves vestibular function, and whether GPR156 has other roles besides orienting hair cells. We find that otolith organs in Gpr156 mouse mutants have normal zonal organization and normal type I-II hair cell distribution and mechano- electrical transduction properties. In contrast, gpr156 zebrafish mutants lack the smaller mechan- ically evoked signals that characterize Emx2-positive hair cells. Loss of GPR156 does not affect orientation- selectivity of afferents in mouse utricle or zebrafish neuromasts. Consistent with normal otolith organ anatomy and afferent selectivity, Gpr156 mutant mice do not show overt vestibular dysfunction. Instead, performance on two tests that engage otolith organs is significantly altered – swimming and off-vertical-axis rotation. We conclude that GPR156 relays hair cell orientation and transduction information downstream of EMX2, but not selectivity for direction-specific afferents. These results clarify how molecular mechanisms that confer bi-directionality to sensory organs contribute to function, from single hair cell physiology to animal behavior.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.