The neural cell adhesion molecules L1 and NCAM-180 act in different steps of neurite outgrowth

The formation of neurocircuitry depends on the control of neurite outgrowth that, in turn, can be divided into two processes: nerve growth cone protru sion and neurite extension. It has long been known that the neural cell adh esion molecules L1 and NCAM-180 promote neurite outgrowth, but how they fun ction in growth cones is unclear. We addressed the roles of L1 and NCAM-180 in neurite outgrowth by using microscale chromophore-assisted laser inacti vation (micro-CALI) of these proteins to perturb their functions at precise times in single growth cones of embryonic chick dorsal root ganglion neuro ns grown in culture. Micro-CALI of L1 causes neurite retraction after a 10 min lag period but does not affect growth cone protrusion. In contrast, mic ro-CALI of NCAM-180 causes rapid growth cone retraction but does not affect neurite extension. The simultaneous inactivation of both these molecules r esulted in both distinct effects that were segregated in time. The behavior of growth cones after these micro-CALI treatments resemble the drug-induce d perturbation of microtubules for L1 and F-actin for NCAM-180. These findi ngs suggest distinct roles in the growth cone for L1 and NCAM-180 in differ ent steps of neurite outgrowth: L1 functions in neurite extension, whereas NCAM-180 functions in growth cone protrusion.