The TrkC subfamily of primary high-affinity neurotrophin-3 receptors is composed of catalytic (kinase-containing; TrkC K) and noncatalytic (TrkC NC) isoforms generated by alternative splicing. We previously reported the presence of the mouse noncatalytic TrkC NC2 isoform in regions of neuronal differentiation [Menn, B., Timsit, S., Calothy, G. & Lamballe, F. (1998) J. Comp. Neurol., 401, 47-64]. In order to gain insight into specific roles for TrkC NC2 receptors during CNS neurogenesis, we compared its distribution with that of its catalytic counterparts and the p75NTR receptor in in vivo and in vitro model systems of early and late neuronal differentiation. We found that TrkC NC2 expression coincided with the exit of neuronal progenitors from the cell cycle and was maintained in differentiated cerebellar neurons. We also showed that, whilst TrkC K receptors were expressed both in mitotic and postmitotic cells, TrkC NC2 was present only in differentiating neural stem cell progeny, suggesting its involvement in neuronal and glial cell differentiation. During neuritogenesis of primary neocortical neurons, both TrkC isoforms as well as p75NTR were located in axonal and dendritic processes. However, whilst these various receptors were present in the same neuronal compartments, TrkC NC2 distribution was specifically restricted to distinct areas of extending neurites. Taken together, these findings suggest that spatiotemporal localization of the noncatalytic receptor could account for specific local effects of neurotrophin-3.