Disruption of laminin in the peripheral nervous system impedes non-myelinating Schwann cell development and impairs nociceptive sensory function

摘要

The mechanisms controlling the differentiation of immature Schwann cells (SCs) into non-myelinating SCs is not known. Laminins are extracellular matrix proteins critical for myelinating SC differentiation, but their roles in non-myelinating SC development have not been established. Here we show that the peripheral nerves of mutant mice with laminin-deficient SCs do not form Remak bundles, which consist of a single non-myelinating SC interacting with multiple unmyelinated axons. These mutant nerves show aberrant L1 and N-CAM expression pattern during development. The homophilic and heterophilic interactions of N-CAM are also impaired in the mutant nerves. Other molecular markers for non-myelinating SCs, including Egr-1, GFAP, and AN2/NG2, are all absent in adult mutant nerves. Analysis of expression of SC lineage markers demonstrates that non-myelinating SCs do not develop in mutant nerves. Additionally, mutant mice are insensitive to heat stimuli and show a decreased number of C-fiber sensory neurons, indicating reduced nociceptive sensory function. These results show that laminin participates in non-myelinating SC development and Remak bundles and suggest a possible role for laminin deficiency in peripheral sensory neuropathies.