Cadherin‐11 controls otolith assembly: Evidence for extracellular cadherin activity

Abstract

Cadherin-11/Cdh11 is expressed through early development and strongly during inner ear development (otic placode and vesicle). Here we show that antisense knockdown of Cdh11 during early zebrafish development interferes with otolith formation. Immunofluorescence labeling showed that Cdh11 expression was concentrated on and within the otolith. Cdh11 was faintly detected at the lateral surface (sites of cell-cell contact) of otic epithelial cells and in the cytoplasm. Strongly labeled Cdh11 containing puncta were detected within the otolymph (the fluid within the otic vesicle) and associated with the otolith surface. BODIPY-ceramine-labeled vesicular structures detected in the otolymph were larger and more numerous in Cdh11 knockdown embryos. We present evidence supporting a working model that vesicular structures containing Cdh11 (perhaps containing biomineralization components) are exported from the otic epithelium into the otolymph, adhere to one another and to the surface of the growing otolith, facilitating otolith growth.

Fluid flows and forces in development: functions, features and biophysical principles

“…Electron microscopy and time-lapse analyses show that otolith growth starts as a nucleus of spherules aggregating at the top of a tether cilium (Fig. 3F) (Pisam et al, 2002) and suggest that otoliths form through spherule self-aggregation (Clendenon et al, 2009). Spherules are secreted from the apical regions of the epithelial cells that line the inner ear cavity (Riley et al, 1997;Pisam et al, 2002) (Fig.…”

Mechanistic Basis of Otolith Formation during Teleost Inner Ear Development

“…The otic cavity contains precursor 1–3 micron particles, or spherules, secreted from the apical portions of the epithelial cells of the inner ear (Riley et al, 1997). Time lapse analysis and electron microscopy show that otolith growth starts as a nucleus of spherules aggregating at the top of a tether cilium (Clendenon et al, 2009; Pisam et al, 2002). At 30hpf, a mineralized ovoid otolith is visible (Pisam et al, 2002; Sollner et al, 2003) and concentric arrays of spherule deposition are seen at the periphery of the nascent otolith (Pisam et al, 2002).…”

DFNB89, a novel autosomal recessive nonsyndromic hearing impairment locus on chromosome 16q21-q23.2

“…CDH23 (Bork et al 2001) and PCDH15 (Ahmed et al 2003)) and facilitates cell–cell adhesion and signaling in various tissues. The Cadherin 11 gene ( CDH11 ; MIM 600023) was shown to be necessary for otolith assembly in the developing zebra fish embryo (Clendenon et al 2009) and was also reported to be expressed in the human fetal cochlea (Skvorak et al 1999). The Cadherin 1 ( CDH1 ; MIM 192090) localizes to the apical intercellular junctions of supporting cells within the murine organ of Corti suggesting a role in inter-supporting cell adhesion (Whitlon 1993).…”