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

First Author  Ebeid M Year  2023
Journal  PLoS Genet Volume  19
Issue  8 Pages  e1010925
PubMed ID  37639482 Mgi Jnum  J:340392
Mgi Id  MGI:7527973 Doi  10.1371/journal.pgen.1010925
Citation  Ebeid M, et al. (2023) beta-Catenin transcriptional activity is required for establishment of inner pillar cell identity during cochlear development. PLoS Genet 19(8):e1010925
abstractText  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 beta-Catenin is required for establishing IPC identity in the mammalian cochlea. To differentiate the transcriptional and adhesion roles of beta-Catenin in establishing IPC identity, we examined two different models of beta-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 beta-Catenin transcriptional function lost IPCs and displayed extranumerary OPCs, indicating its requirement for establishing IPC identity. Overexpression of beta-Catenin induced proliferation within IPCs but not ectopic IPCs. Single-cell transcriptomes of supporting cells lacking beta-Catenin transcriptional function show a loss of the IPC and gain of OPC signatures. Finally, targeted deletion of beta-Catenin in IPCs also led to the loss of IPC identity, indicating a cell autonomous role of beta-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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