Ten-m3 plays a role in the formation of thalamostriatal projections

The importance of the thalamostriatal pathway for a myriad of brain functions is becoming increasingly apparent. Little is known about the formation of this pathway in mice. Further, while Ten-m3, a member of the Ten-m/teneurin/Odz family, is implicated in the proper wiring of mature thalamostriatal projections, its developmental time course is unknown. Here, we describe the normal development of thalamostriatal projections arising from the parafascicular nucleus (PFN) and show a role for Ten-m3 in its formation. Ten-m3 is expressed in both the PFN and the striatum by embryonic day 17 (E17). By postnatal day 3 (P3), it had a patchy appearance in the striatum, overlaid on a high dorsal-low ventral expression gradient in both structures. In wild-type mice, axons from the PFN begin to innervate the striatum by E17. By P3, terminals had ramified but were not confined to any striatal subregion. By P7, the axons had begun to avoid striosomes. The first indication of clustering of thalamic terminals within the striatal matrix was also seen at this time point. The compartmental targeting and clustering of PFN projections became more apparent by P10. Analysis of Ten-m3 knockout mice showed that while the early developmental progression of the thalamostriatal pathway is conserved, by P10 differences emerged, with a loss of topographic precision and the absence of terminal clustering. No evidence of the involvement of EphA7 downstream of Ten-m3 was found. Overall, our results suggest that Ten-m3 plays a role in the consolidation and refinement of thalamic axons to a specific subregion of the striatal matrix.