Disruption of laminin in the peripheral nervous system impedes nonmyelinating Schwann cell development and impairs nociceptive sensory function.
The mechanisms controlling the differentiation of immature Schwann cells (SCs) into nonmyelinating SCs is not known. Laminins are extracellular matrix proteins critical for myelinating SC differentiation, but their roles in nonmyelinating 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 nonmyelinating SC interacting with multiple unmyelinated axons. These mutant nerves show aberrant L1 and neural cell adhesion molecule (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 nonmyelinating SCs, including Egr-1, glial fibrillary acidic protein, and AN2/NG2, are all absent in adult mutant nerves. Analysis of expression of SC lineage markers demonstrates that nonmyelinating 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 nonmyelinating SC development and Remak bundle formation and suggest a possible role for laminin deficiency in peripheral sensory neuropathies.
Yu
Wei-Ming
WM
Laboratory of Neurobiology and Genetics, The Rockefeller University, New York, NY, USA.
Yu
Huaxu
H
Chen
Zu-Lin
ZL
Strickland
Sidney
S
D000818:Animals; D000941:Antigens / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007797:Laminin / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D016253:Microscopy, Immunoelectron / Q000379:methods; D052066:N-Ethylmaleimide-Sensitive Proteins / Q000235:genetics / Q000378:metabolism; D036421:Nerve Fibers, Unmyelinated / Q000502:physiology* / Q000648:ultrastructure; D019006:Neural Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D050816:Octamer Transcription Factor-6 / Q000378:metabolism; D017933:Peripheral Nervous System / Q000166:cytology* / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058477:Receptors, Purinergic P2X3; D012583:Schwann Cells / Q000502:physiology* / Q000648:ultrastructure; D011984:Sensory Receptor Cells / Q000378:metabolism / Q000648:ultrastructure; D020886:Somatosensory Disorders / Q000235:genetics / Q000503:physiopathology*; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D015740:Calcitonin Gene-Related Peptide; D005904:Glial Fibrillary Acidic Protein; D007797:Laminin; D052066:N-Ethylmaleimide-Sensitive Proteins; D019006:Neural Cell Adhesion Molecules; D050816:Octamer Transcription Factor-6; D011509:Proteoglycans; D018048:Receptors, Purinergic P2; D058477:Receptors, Purinergic P2X3; D000099216:Chondroitin Sulfate Proteoglycan 4; C546409:P2rx3 protein, mouse; C089141:laminin gamma 1