β-Catenin transcriptional activity is required for establishment of inner pillar cell identity during cochlear development.

The mammalian cochlea is composed of sensory hair cells as well as multiple different types of non-sensory supporting cells. Pillar cells are one type of supporting cell that form the tunnel of Corti and include two morphologically and functionally distinct subtypes: inner pillar cells (IPCs) and ou...

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Main Authors: Michael Ebeid, Ippei Kishimoto, Pooja Roy, Mohd Ali Abbas Zaidi, Alan G Cheng, Sung-Ho Huh
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2023-08-01
Series:PLoS Genetics
Online Access:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1010925&type=printable
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author Michael Ebeid
Ippei Kishimoto
Pooja Roy
Mohd Ali Abbas Zaidi
Alan G Cheng
Sung-Ho Huh
author_facet Michael Ebeid
Ippei Kishimoto
Pooja Roy
Mohd Ali Abbas Zaidi
Alan G Cheng
Sung-Ho Huh
author_sort Michael Ebeid
collection DOAJ
description The mammalian cochlea is composed of sensory hair cells as well as multiple different types of non-sensory supporting cells. Pillar cells are one type of supporting cell that form the tunnel of Corti and include two morphologically and functionally distinct subtypes: inner pillar cells (IPCs) and outer pillar cells (OPCs). The processes of specification and differentiation of inner versus outer pillar cells are still unclear. Here, we show that β-Catenin is required for establishing IPC identity in the mammalian cochlea. To differentiate the transcriptional and adhesion roles of β-Catenin in establishing IPC identity, we examined two different models of β-Catenin deletion; one that deletes both transcriptional and structural functions and one which retains cell adhesion function but lacks transcriptional function. Here, we show that cochleae lacking β-Catenin transcriptional function lost IPCs and displayed extranumerary OPCs, indicating its requirement for establishing IPC identity. Overexpression of β-Catenin induced proliferation within IPCs but not ectopic IPCs. Single-cell transcriptomes of supporting cells lacking β-Catenin transcriptional function show a loss of the IPC and gain of OPC signatures. Finally, targeted deletion of β-Catenin in IPCs also led to the loss of IPC identity, indicating a cell autonomous role of β-Catenin in establishing IPC identity. As IPCs have the capacity to regenerate sensory hair cells in the postnatal cochlea, our results will aid in future IPC-based hair cell regeneration strategies.
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spelling doaj-art-4eaa9e2f51a642d1a8ee9f3c648feafd2025-07-25T05:31:06ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042023-08-01198e101092510.1371/journal.pgen.1010925β-Catenin transcriptional activity is required for establishment of inner pillar cell identity during cochlear development.Michael EbeidIppei KishimotoPooja RoyMohd Ali Abbas ZaidiAlan G ChengSung-Ho HuhThe mammalian cochlea is composed of sensory hair cells as well as multiple different types of non-sensory supporting cells. Pillar cells are one type of supporting cell that form the tunnel of Corti and include two morphologically and functionally distinct subtypes: inner pillar cells (IPCs) and outer pillar cells (OPCs). The processes of specification and differentiation of inner versus outer pillar cells are still unclear. Here, we show that β-Catenin is required for establishing IPC identity in the mammalian cochlea. To differentiate the transcriptional and adhesion roles of β-Catenin in establishing IPC identity, we examined two different models of β-Catenin deletion; one that deletes both transcriptional and structural functions and one which retains cell adhesion function but lacks transcriptional function. Here, we show that cochleae lacking β-Catenin transcriptional function lost IPCs and displayed extranumerary OPCs, indicating its requirement for establishing IPC identity. Overexpression of β-Catenin induced proliferation within IPCs but not ectopic IPCs. Single-cell transcriptomes of supporting cells lacking β-Catenin transcriptional function show a loss of the IPC and gain of OPC signatures. Finally, targeted deletion of β-Catenin in IPCs also led to the loss of IPC identity, indicating a cell autonomous role of β-Catenin in establishing IPC identity. As IPCs have the capacity to regenerate sensory hair cells in the postnatal cochlea, our results will aid in future IPC-based hair cell regeneration strategies.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1010925&type=printable
spellingShingle Michael Ebeid
Ippei Kishimoto
Pooja Roy
Mohd Ali Abbas Zaidi
Alan G Cheng
Sung-Ho Huh
β-Catenin transcriptional activity is required for establishment of inner pillar cell identity during cochlear development.
PLoS Genetics
title β-Catenin transcriptional activity is required for establishment of inner pillar cell identity during cochlear development.
title_full β-Catenin transcriptional activity is required for establishment of inner pillar cell identity during cochlear development.
title_fullStr β-Catenin transcriptional activity is required for establishment of inner pillar cell identity during cochlear development.
title_full_unstemmed β-Catenin transcriptional activity is required for establishment of inner pillar cell identity during cochlear development.
title_short β-Catenin transcriptional activity is required for establishment of inner pillar cell identity during cochlear development.
title_sort β catenin transcriptional activity is required for establishment of inner pillar cell identity during cochlear development
url https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1010925&type=printable
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AT poojaroy bcatenintranscriptionalactivityisrequiredforestablishmentofinnerpillarcellidentityduringcochleardevelopment
AT mohdaliabbaszaidi bcatenintranscriptionalactivityisrequiredforestablishmentofinnerpillarcellidentityduringcochleardevelopment
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