Gene targeting reveals the role of Oc90 as the essential organizer of the otoconial organic matrix.
A critical part of the functional development of our peripheral balance system is the embryonic formation of otoconia, composite crystals that overlie and provide optimal stimulus input to the sensory epithelium of the gravity receptor in the inner ear. To date neither the functions of otoconial proteins nor the processes of crystal formation are clearly defined. Using gene targeting and protein analysis strategies, we demonstrate that the predominant mammalian otoconin, otoconin-90/95 (Oc90), is essential for formation of the organic matrix of otoconia by specifically recruiting other matrix components, which includes otolin, a novel mammalian otoconin that we identified to be in wildtype murine otoconia. We show that this matrix controls otoconia growth and morphology by embedding the crystallites during seeding and growth. During otoconia development, the organic matrix forms prior to CaCO3 deposition and provides optimal calcification efficiency. Histological and ultrastructural examinations show normal inner ear epithelial morphology but reduced acellular matrices, including otoconial, cupular and tectorial membranes, in Oc90 null mice, likely due to an absence of Oc90 and a profound reduction of otolin. Our data demonstrate the critical roles of otoconins in otoconia seeding, growth and anchoring and suggest mechanistic similarities and differences between otoconia and bone calcification.
Zhao
Xing
X
Genetics Department, Boys Town National Research Hospital, Omaha, NE 68131, and Center for Neuroscience, Communication Science Program, University of California at Davis 95616, USA.
Yang
Hua
H
Yamoah
Ebenezer N
EN
Lundberg
Yunxia Wang
YW
D000818:Animals; D002113:Calcification, Physiologic; D002135:Calcium-Binding Proteins; D007758:Ear, Inner / Q000196:embryology* / Q000254:growth & development / Q000648:ultrastructure; D004848:Epithelium / Q000196:embryology / Q000254:growth & development / Q000648:ultrastructure; D016326:Extracellular Matrix Proteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008855:Microscopy, Electron, Scanning; D010037:Otolithic Membrane / Q000196:embryology* / Q000254:growth & development / Q000648:ultrastructure; D014961:X-Ray Diffraction
D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; C512837:Oc90 protein, mouse