Heterophilic binding of L1 on unmyelinated sensory axons mediates schwann cell adhesion and is required for axonal survival

This study investigated the function of the adhesion molecule L1 in unmyeli nated fibers of the peripheral nervous system (PNS) by analysis of L1-defic ient mice. We demonstrate that L1 is present on axons and Schwann cells of sensory unmyelinated fibers, but only on Schwann cells of sympathetic unmye linated fibers. In L1-deficient sensory nerves, Schwann cells formed but fa iled to retain normal axonal ensheathment. L1-deficient mice had reduced se nsory function and loss of unmyelinated axons, while sympathetic unmyelinat ed axons appeared normal. In nerve transplant studies, loss of axonal-L1, b ut not Schwann cell-L1, reproduced the L1-deficient phenotype. These data e stablish that heterophilic axonal-L1 interactions mediate adhesion between unmyelinated sensory axons and Schwann cells, stabilize the polarization of Schwann cell surface membranes, and mediate a trophic effect that assures axonal survival.