Extracellular matrix (ECM) is composed of collagens, glycoproteins, and carbohydrates and exhibits sophisticated ultrastructure and highly-ordered architecture. To understand the morphogenesis mechanism of complex ECM, we studied the development of the tectorial membrane (TM), a specialized ECM in an inner ear, which plays important roles in frequency tuning and amplification of auditory stimuli. The TM is formed by cochlear supporting cells and hovers over the organ of Corti. Its exquisite architecture and unique position in an open luminal space of the scala media suggest that there should exist a mechanism to prevent the diffusion of the TM components and to organize the ultrastructure. Alpha-tectorin (Tecta) is the major non-collagenous protein of the TM and plays roles in crosslinking collagens and other TM components. We showed that Tecta is tethered to the surface membrane via a GPI-anchorage. Conversion of Tecta into a secreted form in vivo leads to disorganized aggregation of collagen fibrils, which is detached from the producing cells and lacks glycoproteins. Secreted soluble Tecta that is not clustered into the TM network is uptaken by CD45+ phagocytes in the stria vascularis. On the other hand, conversion of Tecta into a transmembrane protein generates a thin layer of collagen network on the supporting cells, which does not grow. Excessive collages that are not captured on the cell surface form disorganized aggregates. Our study reveals the dual roles of GPI-anchorage of Tecta in TM development: surface tethering of Tecta is required for the organization of collagen networks and GPI-dependent release of Tecta mediates the growth of the TM. We propose a three-dimensional (3D) printing model for the morphogenesis of the complex ECM: a stepwise layering of a new collagen network by a surface organizer between the pre-established complex and the cell surface.

3D-printing model for ECM morphogenesis: Dual roles of a GPI-anchored structural organizer in the formation and layering of the complex ECM

2019 Spring National Meeting

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