Remak bundle size, structure, and function are regulated by the Schwann cell basal lamina

Remak bundles are groups of small-diameter unmyelinated nociceptive axons ensheathed by Schwann cells (SCs). Whereas the development and maturation of myelinating SCs have been extensively studied, the formation of Remak bundles remains poorly understood. By preventing the secretion of type IV collagen from SCs, we observe normal myelin but abnormal Remak bundles. There is a decrease in Remak bundle density, an increase in bundle size, improperly ensheathed axons, and a decrease in mechanosensitivity. While Remak bundle formation appears to be independent of integrin signaling, the loss of type IV collagen leads to a decrease in postnatal SC proliferation. Inducing the emergence of supernumerary SCs rescues Remak bundle architecture and mechanosensitivity. Taken together, our results demonstrate that SC-secreted basal lamina critically regulates Remak SC number, bundle size, and structure. Our findings provide insight into the functional role of Remak bundles and highlight their potential involvement in peripheral neuropathies and neuropathic pain.