Naimi’s Structure and Migration: A Tissue-Specific Pattern of Organization Discovered in Normal Bladder Urothelia

Abstract

Introduction: Sequential migration and organization are critical events in tissue development. The urothelium, the epithelium lining urologic tissues, is highly specialized regarding the watertight function and adaptation to large and frequent changes in urine volume. To establish the functional state of this tissue, horizontal cells growth is required to allow the vertical development into a multilayered uroepithelium. If this first step is already documented, the mechanism implicated in the switch toward the vertical growth is not yet described. Methods: We had elaborated a three-dimensional bladder model, made of bladder mesenchymal cells (BMC) seeded in a collagen matrix which can promote bladder urothelial cells (BUC) development. Results: This in vitro model allowed us to discover a behavior specific to BUC, resulting in a specific urothelial stratification and differentiation pattern. Cellular alignment into a circular arrangement, named Naimi’s structure, followed by coordinated gyratory cellular movement, named Naimi’s migration, were sequentially observed in our in vitro model and were also confirmed in native bladder Conclusion: We describe here the steps that led to Naimi’s structure and migration. Ultrastructural observations are also provided to document the remarkable organization of urothelial cells and the underlying mesenchymal rearrangement. Keywords: Urinary bladder; Urothelium; Cell migration; Extracellular matrix