Abstract
SummaryThe cochlear sensory epithelium contains a functionally important triangular fluid-filled space between adjacent pillar cells referred to as the tunnel of Corti. However, the molecular mechanisms leading to local cell-cell separation during development remain elusive. Here we show that EphA4 associates with ADAM10 to promote the destruction of E-cadherin-based adhesions between adjacent pillar cells. These cells fail to separate from each other, and E-cadherin abnormally persists at the pillar cell junction in EphA4 forward-signaling-deficient mice, as well as in the presence of ADAM10 inhibitor. Using immunolabeling and an in situ proximity ligation assay, we found that EphA4 forms a complex with E-cadherin and its sheddase ADAM10, which could be activated by ephrin-B2 across the pillar cell junction to trigger the cleavage of E-cadherin. Altogether, our findings provide a new molecular insight into the regulation of adherens junctions, which might be extended to a variety of physiological or pathological processes.
Highlights
In mammals, sounds are perceived through mechanosensory hair cells located in the sensory epithelium of the cochlea
By combining immunolabeling and an in situ proximity ligation assay, we found that EphA4 forms a complex with E-cadherin and its sheddase ADAM10, which could be activated by ephrin-B2 across the pillar cells (PCs) junction to trigger the cleavage of E-cadherin
EphA4 and Ephrin-B2 Are Co-expressed on Both Sides of the inner PCs (IPCs)/outer PCs (OPCs) Junction At immature stages, all cells of the organ of Corti are closely connected and the IPCs abut on the OPCs (Figure 1A)
Summary
Sounds are perceived through mechanosensory hair cells located in the sensory epithelium of the cochlea (the organ of Corti). The organ of Corti contains one row of inner hair cells and three rows of outer hair cells separated by two parallel rows of non-sensory pillar cells (PCs). The somatic motility of outer hair cells produces oscillatory fluid flow in the tunnel of Corti, which is critical for cochlear amplification (Karavitaki and Mountain, 2007). A critical step should be the progressive loss of the adhesion protein E-cadherin from the lateral membranes of the PCs (Johnen et al, 2012; Whitlon, 1993) (Figure 1)
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