부산대학교 도서관

During development, Schwann cells extend lamellipodia-like processes to segregate large- and small-caliber axons during the process of radial sorting. Radial sorting is a prerequisite for myelination and is arrested in human neuropathies because of laminin deficiency. Experiments in mice using targeted mutagenesis have confirmed that laminins 211, 411, and receptors containing theβ1 integrin subunit are required for radial sorting; however, which of the 11α integrins that can pair withβ1 forms the functional receptor is unknown. Here we conditionally deleted all the α subunits that form predominant laminin-binding β1 integrins in Schwann cells and show that only α6β1 and α7β1 integrins are required and that α7β1 compensates for the absence of α6β1 during development. The absence of either α7β1 orα6β1 integrin impairs the ability of Schwann cells to spread and to bind laminin 211 or 411, potentially explaining the failure to extend cytoplasmic processes around axons to sort them. However, doubleα6/α7 integrin mutants show only a subset of the abnormalities found in mutants lacking allβ1 integrins, and a milder phenotype. Double-mutant Schwann cells can properly activate all the major signaling pathways associated with radial sorting and show normal Schwann cell proliferation and survival. Thus,α6β1 andα7β1 are the laminin-binding integrins required for axonal sorting, but other Schwann cellβ1 integrins, possibly those that do not bind laminins, may also contribute to radial sorting during peripheral nerve development. [ABSTRACT FROM AUTHOR]