Role of Nrp1 in controlling cortical interhemispheric circuits

Abstract Callosal projections establish topographically organized maps between cortical areas. Neuropilin-1 (Nrp1) cortical gradient induces an early segregation of developing callosal axons. We investigated later roles of Nrp1 on the development of callosal projections from layer (L) 2/3 of the primary (S1) and secondary (S2) somatosensory (SS) areas, which express higher and lower levels of Nrp1, respectively. We used in utero electroporation to knock down or overexpress Nrp1 combined with retrograde tracers, to map connections at postnatal day 16 and 30. High levels of Nrp1 blocked contralateral S2 innervation while promoted the late postnatal growth of homotopic S1L2/3 and heterotopic S2L2/3 branches into S1. Conversely, knocking down Nrp1 increased the growth of heterotopic S1L2/3 projections into S2, and the overall refinement of S2L2/3 branches, thereby diminishing the number of P30 S2L2/3 callosally projecting neurons. Thus, the Nrp1 gradient determines homotopic SSL2/3 callosal connectivity by regulating late postnatal branching and refinement in a topographic manner.