Abstract
The Wnt/β-catenin signaling pathway plays important roles in mammalian inner ear development. Lgr5, one of the downstream target genes of the Wnt/β-catenin signaling pathway, has been reported to be a marker for inner ear hair cell progenitors. Lgr6 shares approximately 50% sequence homology with Lgr5 and has been identified as a stem cell marker in several organs. However, the detailed expression profiles of Lgr6 have not yet been investigated in the mouse inner ear. Here, we first used Lgr6-EGFP-Ires-CreERT2 mice to examine the spatiotemporal expression of Lgr6 protein in the cochlear duct during embryonic and postnatal development. Lgr6-EGFP was first observed in one row of prosensory cells in the middle and basal turn at embryonic day 15.5 (E15.5). From E18.5 to postnatal day 3 (P3), the expression of Lgr6-EGFP was restricted to the inner pillar cells (IPCs). From P7 to P15, the Lgr6-EGFP expression level gradually decreased in the IPCs and gradually increased in the inner border cells (IBCs). At P20, Lgr6-EGFP was only expressed in the IBCs, and by P30 Lgr6-EGFP expression had completely disappeared. Next, we demonstrated that Wnt/β-catenin signaling is required to maintain the Lgr6-EGFP expression in vitro. Finally, we demonstrated that the Lgr6-EGFP-positive cells isolated by flow cytometry could differentiate into myosin 7a-positive hair cells after 10 days in-culture, and this suggests that the Lgr6-positive cells might serve as the hair cell progenitor cells in the cochlea.
Highlights
The mammalian inner ear cochlea is a very sophisticated organ
We took advantage of the Lgr6-EGFP-Ires-CreERT2 transgenic mice in which EGFP-IresCreERT2 is inserted into the transcriptional start site of the Lgr6 gene
Lgr6 was first observed at E15.5 in one row of Sox2-positive progenitor cells
Summary
The mammalian inner ear cochlea is a very sophisticated organ. The organ of Corti in the inner ear is responsible for hearing in mammals and contains two types of mechanosensory hair cells (inner hair cells and outer hair cells) and six types of supporting cells [Deiters’ cells, Hensen’s cells, Claudius’ cells, pillar cells, inner phalangeal cells, and inner border cells (IBCs)] (Chai et al, 2012). During the development of the mouse cochlea, the otic placode—which will give rise to the auditory and vestibular sensory organs. The placode invaginates to form the otocyst on E11 By this time, the regions that will give rise to sensory neuroepithelia have already been specified (Morsli et al, 1998). At E12, the progenitors of hair cells and supporting cells are still dividing (Ruben, 1967). By E14, all progenitor cells of the inner ear have exited the cell cycle (Ruben, 1967; Lee et al, 2006). Hair cell differentiation first appears in the mid-basal region of the cochlea at E13.5 and spreads bidirectionally during the development of the organ of Corti (Chen et al, 2002). Hair cell differentiation finishes between E17 and E18 (Sher, 1971; Li and Ruben, 1979; Lim and Anniko, 1985; Chen et al, 2002)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
