Merosin promotes neurite growth and Schwann cell migration in vitro and nerve regeneration in vivo: evidence using an antibody to merosin, ARM-1.

Monoclonal antibodies that block the cellular function(s) of specific antigens can provide valuable probes for in vitro and in vivo bioassays. With the goal of understanding the molecular basis of neuron-Schwann cell interactions during development and regeneration, we have sought antibodies that interfere with the function of merosin, the predominant laminin isoform present in the Schwann cell basement membrane. To identify the biological functions of merosin in the peripheral nervous system, we studied Schwann cell migration and neurite outgrowth in vitro and nerve regeneration in vivo, in the presence and the absence of a monoclonal antibody that we believe binds to merosin, ARM-1 (Anti Rodent Merosin-1). The ARM-1 antibody blocked both neurite outgrowth and Schwann cell migration in vitro. This antibody also reduced neuritic branching in vitro. In vivo, the ARM-1 antibody blocked the regeneration of sympathetic nerve fibers in the rat iris. The blockade of neurite outgrowth and Schwann cell migration by ARM-1 antibody suggests that merosin is involved in facilitating the two most critical cellular events during the normal development and regeneration of peripheral nerves, i.e., axon growth and Schwann cell migration. Furthermore, the regulation of both Schwann cell migration and axon growth by the ARM-1 antigen implies that these two cellular events obey a common set of molecular signals during the development and regeneration of peripheral nerves.