β-Catenin is required for radial cell patterning and identity in the developing mouse cochlea

• Published in: Proceedings of the National Academy of Sciences - PNAS 2019-10, Vol.116 (42), p.21054-21060
• Main Authors: Jansson, Lina, Ebeid, Michael, Shen, Jessica W., Mokhtari, Tara E., Quiruz, Lee A., Ornitz, David M., Huh, Sung-Ho, Cheng, Alan G.
• Format: Article
• Language: English
• Subjects: Ablation; Adhesion; Animal models; Animals; beta Catenin - metabolism; Biological Sciences; Biomarkers - metabolism; Cell adhesion; Cell adhesion & migration; Cell Adhesion - physiology; Cell density; Cell differentiation; Cell Differentiation - physiology; Clonal deletion; Cochlea; Cochlea - metabolism; Cochlea - physiology; Differentiation (biology); Embryogenesis; Embryonic growth stage; Fibroblast growth factor 8; Fibroblast growth factor receptors; Gene Expression Regulation, Developmental - physiology; Hair; Hair cells; Hair Cells, Auditory - metabolism; Hair Cells, Auditory - physiology; Hair Cells, Auditory, Inner - metabolism; Hair Cells, Auditory, Inner - physiology; Hearing protection; Mice; Organ of Corti; Organ of Corti - metabolism; Organogenesis - physiology; Organs; Outer hair cells; Pattern formation; Specifications; Transcription; β-catenin
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1910223116

Development of multicellular organs requires the coordination of cell differentiation and patterning. Critical for sound detection, the mammalian organ of Corti contains functional units arranged tonotopically along the cochlear turns. Each unit consists of sensory hair cells intercalated by nonsensory supporting cells, both specified and radially patterned with exquisite precision during embryonic development. However, how cell identity and radial patterning are jointly controlled is poorly understood. Here we show that β-catenin is required for specification of hair cell and supporting cell subtypes and radial patterning of the cochlea in vivo. In 2 mouse models of conditional β-catenin deletion, early specification of Myosin7-expressing hair cells and Prox1-positive supporting cells was preserved. While β-catenin-deficient cochleae expressed FGF8 and FGFR3, both of which are essential for pillar cell specification, the radial patterning of organ of Corti was disrupted, revealed by aberrant expression of cadherins and the pillar cell markers P75 and Lgr6. Moreover, β-catenin ablation caused duplication of FGF8-positive inner hair cells and reduction of outer hair cells without affecting the overall hair cell density. In contrast, in another transgenic model with suppressed transcriptional activity of β-catenin but preserved cell adhesion function, both specification and radial patterning of the organ of Corti were intact. Our study reveals specific functions of β-catenin in governing cell identity and patterning mediated through cell adhesion in the developing cochlea.