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Tmc proteins are essential for zebrafish hearing where Tmc1 is not obligatory.
- Source :
-
Human molecular genetics [Hum Mol Genet] 2020 Jul 29; Vol. 29 (12), pp. 2004-2021. - Publication Year :
- 2020
-
Abstract
- Perception of sound is initiated by mechanically gated ion channels at the tips of stereocilia. Mature mammalian auditory hair cells require transmembrane channel-like 1 (TMC1) for mechanotransduction, and mutations of the cognate genetic sequences result in dominant or recessive heritable deafness forms in humans and mice. In contrast, zebrafish lateral line hair cells, which detect water motion, require Tmc2a and Tmc2b. Here, we use standard and multiplex genome editing in conjunction with functional and behavioral assays to determine the reliance of zebrafish hearing and vestibular organs on Tmc proteins. Surprisingly, our approach using multiple mutant alleles demonstrates that hearing in zebrafish is not dependent on Tmc1, nor is it fully dependent on Tmc2a and Tmc2b. Hearing however is absent in triple-mutant zebrafish that lack Tmc1, Tmc2a and Tmc2b. These outcomes reveal a striking resemblance of Tmc protein reliance in the vestibular sensory epithelia of mammals to the maculae of zebrafish. Moreover, our findings disclose a logic of Tmc use where hearing depends on a complement of Tmc proteins beyond those employed to sense water motion.<br /> (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Subjects :
- Animals
Deafness genetics
Deafness pathology
Hair Cells, Auditory metabolism
Hair Cells, Auditory pathology
Hair Cells, Auditory, Inner metabolism
Hair Cells, Auditory, Inner pathology
Hearing Loss, Sensorineural pathology
Humans
Mechanotransduction, Cellular genetics
Mice
Mutation genetics
Stereocilia genetics
Stereocilia pathology
Zebrafish genetics
Hearing genetics
Hearing Loss, Sensorineural genetics
Membrane Proteins genetics
Zebrafish Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2083
- Volume :
- 29
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Human molecular genetics
- Publication Type :
- Academic Journal
- Accession number :
- 32167554
- Full Text :
- https://doi.org/10.1093/hmg/ddaa045